Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
long-tailed macaque response to deforestation in a plasmodium knowlesi-endemic area.land-use changes can impact infectious disease transmission by increasing spatial overlap between people and wildlife disease reservoirs. in malaysian borneo, increases in human infections by the zoonotic malaria plasmodium knowlesi are hypothesised to be due to increasing contact between people and macaques due to deforestation. to explore how macaque responses to environmental change impact disease risks, we analysed movement of a gps-collared long-tailed macaque in a knowlesi-endemic area in ...201930927165
a unique b cell epitope-based particulate vaccine shows effective suppression of hepatitis b surface antigen in mice.this study aimed to develop a novel therapeutic vaccine based on a unique b cell epitope and investigate its therapeutic potential against chronic hepatitis b (chb) in animal models.202030926653
immunohistological study of monkey foveal retina.the fovea centralis, an anatomically concave pit located at the center of the macula, is avascular, hypoxic, and characteristic of stem-cell niches of other tissues. we hypothesized that in the fovea, undifferentiated retinal-stem-cell-like cells may exist, and that neurogenesis may occur. hence, we performed an immunohistological study using cynomolgus monkey retinas. after preparing frozen tissue sections of the retina including the foveal pit, immunostaining was performed for glial fibrillary ...201930918305
targeting multiple myeloma with amg 424, a novel anti-cd38/cd3 bispecific t-cell-recruiting antibody optimized for cytotoxicity and cytokine release.despite advances in the treatment of multiple myeloma, new therapies are needed to induce more profound clinical responses. t-cell-redirected lysis triggered by bispecific antibodies recruiting t cells to cancer cells is a clinically validated mechanism of action against hematologic malignancies and cd38 is a tumor-associated antigen with near-universal expression in multiple myeloma. thus, an anti-cd38/cd3 bispecific t-cell-recruiting antibody has the potential to be an effective new therapeuti ...201930918018
effects of the cathepsin k inhibitor ono-5334 and concomitant use of ono-5334 with methotrexate on collagen-induced arthritis in cynomolgus monkeys.we examined whether the cathepsin k inhibitor, ono-5334, administered alone or in combination with methotrexate (mtx), could ameliorate joint destruction evoked by collagen-induced arthritis (cia) in female cynomolgus monkeys. cia was induced by immunizing with bovine type ii collagen. ono-5334 (30 mg/kg/day) was orally administered once daily and mtx (10 mg/body/day) twice weekly for 9 weeks. x-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal ...201930906325
granulovacuolar degeneration in brains of senile cynomolgus monkeys.neurons with histopathological changes consistent with granulovacuolar degeneration (gvd) were found in brain sections from aged cynomolgus monkeys (macaca fascicularis) with clinical and pathological signs of cognitive aging. to our knowledge, this is the first reported description of gvd in non-human primates. gvd-like lesions were found also in age-matched cognitively healthy subjects, albeit in lower numbers, suggesting that they may relate to aging and the increase may have tendency to incr ...201930899220
toxicologic pathology forum*: opinion on sexual maturity and fertility assessment in long-tailed macaques ( macaca fascicularis) in nonclinical safety studies.if nonhuman primates represent the only relevant species for nonclinical safety evaluation of biotechnology-derived products, male and female fertility effects can be assessed in repeat dose toxicity studies given that sexually mature monkeys are used. this opinion piece provides recommendations for determining sexual maturity and when/how fertility assessments should be conducted in the cynomolgus monkey. male sexual maturity should be proven by presence of sperm in a semen sample, female sexua ...201930898082
phenotypic distinctions between the nodose and jugular trpv1-positive vagal sensory neurons in the cynomolgus monkey.vagal capsaicin-sensitive afferent c-fibers play an important role in the maintenance of visceral homeostasis and contribute to symptoms in visceral diseases. based on their developmental origin two functionally distinct types of vagal c-fibers are recognized: those with neurons in the vagal nodose ganglia (derived from epibranchial placodes) and in the vagal jugular ganglia (from neural crest). studies in nonprimate species demonstrated that the vagal nodose and jugular c-fibers differ in activ ...201930896676
the pattern of plasma bcaa concentration and liver bckdha gene expression in gk rats during t2d progression.this study was conducted to measure the concentration of branched chain amino acid (bcaa) in different species and detect the expression pattern of the liver bckdha gene in goto-kakizaki (gk) rats during type 2 diabetes (t2d) progression.201830891580
effects of tanezumab on satellite glial cells in the cervicothoracic ganglion of cynomolgus monkeys: a 26-week toxicity study followed by an 8-week recovery period.tanezumab, a humanized monoclonal anti-ngf antibody, has demonstrated efficacy and safety profiles in phase iii clinical trials of chronic pain. in a 24-week study in non-human primates, morphological observations of sympathetic ganglia showed decreased ganglia volume, decreased neuronal size, and increased glial cell density compared with controls after 3 tanezumab treatments. using stereological techniques to quantify glial cells, the present 26-week study found no significant difference after ...201930890348
competition is crucial for social comparison processes in long-tailed macaques.humans modulate their self-evaluations and behaviour as a function of conspecific presence and performance. in this study, we tested for the presence of human-like social comparison effects in long-tailed macaques ( macaca fascicularis). the monkeys' task was to extract food from an apparatus by pulling drawers within reach and we measured latency between drawer pulls. subjects either worked on the task with a partner who could access the apparatus from an adjacent cage, worked in the absence of ...201930890067
multivariate profiling of african green monkey and rhesus macaque t lymphocytes.the complexity of immune responses limits the usefulness of univariate methods in answering complex immunology questions. to demonstrate the utility of a multivariate approach, we employ such approach to compare t cells of african green monkeys (agms) and rhesus macaques (rms). among the most prominent distinguishing features we found were lower cd3 and higher cd28 surface expression in agms compared to rms. after in vitro stimulation, a larger proportion of agm t cells secreted cytokines, espec ...201930886198
an lc-ms/ms approach to assess total and free protein target in the serum of cynomolgus monkey.develop lc-ms/ms-based assays to measure total and free complement c5 in cynomolgus monkey serum as a target engagement biomarker for pharmacokinetic/pharmacodynamic correlation study. materials & methods/results: the c5-specific signature peptide derived from pellet digestion of serum proteins with and without prior immunodepletion of the drug-bound c5 by protein a beads was quantified to assess free and total c5 levels, respectively. conditions for immunodepletion by protein a were optimized t ...201930874444
therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate zt/g4-mmae targeting ron receptor tyrosine kinase for cancer therapy.aberrant expression of the ron receptor tyrosine kinase is a pathogenic feature and a validated drug target in various types of cancers. currently, therapeutic antibodies targeting ron for cancer therapy are under intensive evaluation. here we report the development and validation of a novel humanized anti-ron antibody-drug conjugate for cancer therapy.201930871619
comprehensive evaluation of ubiquitous promoters suitable for the generation of transgenic cynomolgus monkeys†.nonhuman primates (nhps) are considered to be the most valuable models for human transgenic (tg) research into disease because human pathology is more closely recapitulated in nhps than rodents. previous studies have reported the generation of tg nhps that ubiquitously overexpress a transgene using various promoters, but it is not yet clear which promoter is most suitable for the generation of nhps overexpressing a transgene ubiquitously and persistently in various tissues. to clarify this issue ...201930869744
safety and toxicology of ocular gene therapy with recombinant aav vector raav.hcnga3 in nonhuman primates.the purpose of this study was to examine the toxicity and side effects of a recombinant adeno-associated virus 8 (aav8) vector, aimed to treat cyclic nucleotide gated channel alpha 3 (cnga3)-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. both groups were divided into subgroups receiving either vehicle only, a low (1 × 1011 vector genomes (vg)), or a hi ...201930864850
tak-071, a muscarinic m1 receptor positive allosteric modulator, attenuates scopolamine-induced quantitative electroencephalogram power spectral changes in cynomolgus monkeys.activation of the muscarinic m1 receptor is a promising approach to improve cognitive deficits associated with cholinergic dysfunction in alzheimer's disease, dementia with lewy bodies, and schizophrenia. tak-071 is an m1-selective positive allosteric modulator that improves cognitive deficits induced by scopolamine, a non-selective muscarinic receptor antagonist, with reduced side effects on gastrointestinal function in rats. in this study, we explored changes in quantitative electroencephalogr ...201930856192
evaluation of the toxicity and neurological effects of fulranumab in adult cynomolgus monkeys.fulranumab, an anti-human nerve growth factor antibody, was evaluated in a series of nonclinical toxicology studies. no treatment effects were observed in adolescent cynomolgus monkeys in standard design, repeat-dose toxicology studies of up to 6 months. adverse effects on the developing nervous system were observed in offspring of pregnant cynomolgus monkeys treated with fulranumab. subsequent studies including detailed morphologic investigations of the nervous system did reveal fulranumab-rela ...202030852923
defining the ecological and evolutionary drivers of plasmodium knowlesi transmission within a multi-scale framework.plasmodium knowlesi is a zoonotic malaria parasite normally residing in long-tailed and pig-tailed macaques (macaca fascicularis and macaca nemestrina, respectively) found throughout southeast asia. recently, knowlesi malaria has become the predominant malaria affecting humans in malaysian borneo, being responsible for approximately 70% of reported cases. largely as a result of anthropogenic land use changes in borneo, vectors which transmit the parasite, along with macaque hosts, are both now f ...201930849978
enhanced transduction of macaca fascicularis hematopoietic cells with chimeric lentiviral vectors.recent marketing approval for genetically engineered hematopoietic stem and t cells bears witness to the substantial improvements in lentiviral vectors over the last two decades, but evaluations of the long-term efficacy and toxicity of gene and cell therapy products will, nevertheless, require further studies in nonhuman primate models. macaca fascicularis monkeys from mauritius have a low genetic diversity and are particularly useful for reproducible drug testing. in particular, they have a ge ...201930848170
poor second ovarian stimulation in cynomolgus monkeys (macaca fascicularis) is associated with the production of antibodies against human follicle-stimulating hormone.cynomolgus monkeys (macaca fascicularis) are a valuable model organism for human disease modeling because human physiology and pathology are closer to those of cynomolgus monkeys than rodents. it has been widely reported that mature oocytes can be recovered from cynomolgus monkeys through ovarian stimulation by human follicle-stimulating hormone (hfsh). however, it is unknown whether mature oocytes can be effectively obtained through a second ovarian stimulation by hfsh. here, we report that som ...201930842351
long-tailed macaques (macaca fascicularis) can use simple heuristics but fail at drawing statistical inferences from populations to samples.human infants, apes and capuchin monkeys engage in intuitive statistics: they generate predictions from populations of objects to samples based on proportional information. this suggests that statistical reasoning might depend on some core knowledge that humans share with other primate species. to aid the reconstruction of the evolution of this capacity, we investigated whether intuitive statistical reasoning is also present in a species of old world monkey. in a series of four experiments, 11 l ...201830839652
functional and molecular characterization of udp-glucuronosyltransferase 2 family in cynomolgus macaques.udp-glucuronosyltransferases (ugts) are essential enzymes metabolizing endogenous and exogenous chemicals. however, characteristics of ugts have not been fully investigated in molecular levels of cynomolgus macaques, one of non-human primates widely used in preclinical drug metabolism studies. in this study, three ugt2a cdnas (ugt2a1, 2a2, and 2a3) were isolated and characterized along with seven ugt2bs previously identified in cynomolgus macaques. several transcript variants were found in cynom ...201930836059
differences in monocyte: lymphocyte ratio and tuberculosis disease progression in genetically distinct populations of macaques.monocyte:lymphocyte ratio (m:l) has been identified as a risk factor in development of tb disease in children and those undergoing treatment for hiv in co-infected individuals. retrospective analysis was performed using m:l data collected from tb modelling studies performed in rhesus macaques of indian genotype (rm), cynomolgus macaque of chinese genotype (ccm) and cynomolgus macaque of mauritian genotype (mcm), which found that the more susceptible populations (rm and mcm) had higher m:l ratios ...201930833652
chronic, low-level oral exposure to marine toxin, domoic acid, alters whole brain morphometry in nonhuman primates.domoic acid (da) is an excitatory neurotoxin produced by marine algae and responsible for amnesiac shellfish poisoning in humans. current regulatory limits (˜0.075-0.1 mg/kg/day) protect against acute toxicity, but recent studies suggest that the chronic consumption of da below the regulatory limit may produce subtle neurotoxicity in adults, including decrements in memory. as da-algal blooms are increasing in both severity and frequency, we sought to better understand the effects of chronic da e ...201930826346
correlation between genotypes and geographic distribution of entamoeba nuttalli isolates from wild long-tailed macaques in central thailand.entamoeba nuttalli found in non-human primates is the phylogenetically closest species to entamoeba histolytica and is potentially pathogenic. however, infection of wild long-tailed macaques (macaca fascicularis) with e. nuttalli has not been found. in this study, the prevalence of entamoeba infections in wild long-tailed macaques was examined in seven locations in six provinces of thailand. the positive rate for e. nuttalli in 214 fecal samples was 43.9% using pcr, but no infection with e. hist ...201930822548
preclinical safety evaluation of the adrenomedullin-binding antibody adrecizumab in rodents, dogs and non-human primates.adrenomedullin (adm) is a vasoactive peptide in sepsis. the non-neutralizing adm-binding antibody adrecizumab improved outcome in animal models of systemic inflammation and sepsis. herein, we evaluated the preclinical safety of adrecizumab in various animal species. first, wistar rats received vehicle, 100, 200 or 400 mg/kg/day of adrecizumab intravenously (n = 20 each) on days 1, 4, 8 and 14. an additional set of rats received vehicle or 400 mg/kg/day (n = 10 each) on the same days and were fol ...201930822437
signature microrna expression profile is associated with lipid metabolism in african green monkey.non-human primates (nhps) are important models of medical research on obesity and cardiovascular diseases. as two of the most commonly used nhps, cynomolgus macaque (cm) and african green monkey (agm) own different capacities in lipid metabolism of which the mechanism is unknown. this study investigated the expression profiles of lipid metabolism-related micrornas (mirnas) in cm and agm and their possible roles in controlling lipid metabolism-related gene expression.201930819205
distinguishing analgesic drugs from non-analgesic drugs based on brain activation in macaques with oxaliplatin-induced neuropathic pain.the antineoplastic agent oxaliplatin is a first-line treatment for colorectal cancer. however, neuropathic pain, characterized by hypersensitivity to cold, emerges soon after treatment. in severe instances, dose reduction or curtailing treatment may be necessary. while a number of potential treatments for oxaliplatin-induced neuropathic pain have been proposed based on preclinical findings, few have demonstrated efficacy in randomized, placebo-controlled clinical studies. this failure could be r ...201930817933
ionis-pkkrx a novel antisense inhibitor of prekallikrein and bradykinin production.kallikrein is the key contact system mediator responsible for the conversion of high-molecular-weight kininogen into the inflammatory vasodilator peptide bradykinin, a process regulated by c1-esterase inhibitor (c1-inh). in hereditary angioedema (hae), genetic mutations result in deficient or dysfunctional c1-inh and dysregulation of the contact system leading to recurrent, sometimes fatal, angioedema attacks. ionis-pkkrx is a second-generation 2'-o-(2-methoxyethyl)-modified chimeric antisense o ...201930817230
pharmacokinetics, tissue distribution, plasma protein binding, and metabolism study of mefunidone, a novel pirfenidone derivative.mefunidone (mfd), a novel derivation of pirfenidone (pfd), exhibits promising anti-renal fibrosis activity. to avoid early development failures and attrition in clinical phase 1, an evaluation of the preclinical pharmacokinetic (pk) properties of mfd was conducted in this study. the absolute bioavailability was evaluated in sprague dawley rats and cynomolgus monkeys, who received an intragastric or intravenous administration at the dose of 31.25 mg/kg and 10 mg/kg, respectively. tissue distribut ...201930815895
paromomycin sulfate is an effective treatment for balantidiasis in captive cynomolgus monkeys.there are few effective antimicrobial agents against balantidium coli infection. the effect of paromomycin sulfate (ps) against b. coli was confirmed in this study of 596 captive cynomolgus monkeys. in several trials, the minimum dose and duration of oral administration of ps were 25 mg/day for 5 + 5 days, with a 2-day withdrawal interval. to facilitate daily ps administration, pumpkin cakes supplemented with ps were made, which not only resulted in precise effects but also increased the efficie ...201930814394
synthesis and evaluation of two new candidate high-affinity full agonist pet radioligands for imaging 5-ht1b receptors.the serotonin 1b receptor subtype is of interest in the pathophysiology and treatment of depression, anxiety, and migraine. over recent years 5-ht1b receptor binding in human brain has been examined with pet using radioligands that are partial but not full agonists. to explore how the intrinsic activity of a pet radioligand may affect imaging performance, two high-affinity full 5-ht1b receptor agonists (az11136118, 4; and az11895987, 5) were selected from a large compound library and radiolabele ...201930811975
characterization of intrathecal cerebrospinal fluid geometry and dynamics in cynomolgus monkeys (macaca fascicularis) by magnetic resonance imaging.recent advancements have been made toward understanding the diagnostic and therapeutic potential of cerebrospinal fluid (csf) and related hydrodynamics. increased understanding of csf dynamics may lead to improved detection of central nervous system (cns) diseases and optimized delivery of csf based cns therapeutics, with many proposed therapeutics hoping to successfully treat or cure debilitating neurological conditions. before significant strides can be made toward the research and development ...201930811449
five years of successful inducible transgene expression following locoregional adeno-associated virus delivery in nonhuman primates with no detectable immunity.anti-transgene immune responses elicited after intramuscular (i.m.) delivery of recombinant adeno-associated virus (raav) have been shown to hamper long-term transgene expression in large-animal models of raav-mediated gene transfer. to overcome this hurdle, an alternative mode of delivery of raav vectors in nonhuman primate muscles has been described: the locoregional (lr) intravenous route of administration. using this injection mode, persistent inducible transgene expression for at least 1 ye ...201930808235
the frequencies of immunosuppressive cells in adipose tissue differ in human, non-human primate, and mouse models.although the metabolic properties of white adipose tissue have been extensively characterized, the tissue's immune properties are now attracting renewed interest. early experiments in a mouse model suggested that white adipose tissue contains a high density of regulatory t cells (tregs), and so it was assumed that all adipose tissue has an immunosuppressive profile-even though the investigation was limited to visceral body fat in relatively old male mice. this observation was also corroborated b ...201930804937
nk cell immune responses differ after prime and boost vaccination.a better understanding of innate responses induced by vaccination is critical for designing optimal vaccines. here, we studied the diversity and dynamics of the nk cell compartment after prime-boost immunization with the modified vaccinia virus ankara using cynomolgus macaques as a model. mass cytometry was used to deeply characterize blood nk cells. the nk cell subphenotype composition was modified by the prime. certain phenotypic changes induced by the prime were maintained over time and, as a ...201930794328
development of an icosl and baff bispecific inhibitor amg 570 for systemic lupus erythematosus treatment.systemic lupus erythematous (sle) is a heterogeneous disease lacking highly effective treatment options. here we tested if targeting both baff and icosl has superior efficacy than single target inhibition in the mouse arthritis and lupus models. we also generated amg 570, an icosl and baff bispecific inhibitory molecule, for potential treatment of autoimmune diseases such as sle.201930789152
phase i study of pf‐04895162, a kv7 channel opener, reveals unexpected hepatotoxicity in healthy subjects, but not rats or monkeys: clinical evidence of disrupted bile acid homeostasis.during a randomized phase 1 clinical trial the drug candidate, pf-04895162 (ica-105665), caused transaminase elevations (≥grade 1) in six of eight healthy subjects treated at 300 mg twice daily for 2-weeks (nct01691274). this was unexpected since studies in rats (<6 months) and cynomolgus monkeys (<9 months) treated up to 100 mg/kg/day did not identify the liver as a target organ. mechanistic studies showed pf-04895162 had low cytotoxic potential in human hepatocytes, but inhibited liver mitocho ...201930784208
characterization, biology, and expansion of regulatory t cells in the cynomolgus macaque for preclinical studies.reliable in vitro expansion protocols of regulatory t cells (tregs) are needed for clinical use. we studied the biology of mauritian cynomolgus macaque (mcm) tregs and developed four in vitro treg expansion protocols for translational studies. tregs expanded 3000-fold when artificial antigen presenting cells (aapcs) expressing human cd80, cd58 and cd32 were used throughout the culture. when donor peripheral blood mononuclear cells (pbmcs) were used as the single source of apcs followed by aapcs, ...201930768842
a novel anti-egfr mab ame55 with lower toxicity and better efficacy than cetuximab when combined with irinotecan.to improve efficacy and minimize toxicity of egfr inhibition treatment, we developed ame55, a novel anti-egfr igg1 with lower affinity to egfr than cetuximab (c225) from a human phage library. ame55 had lower bioactivity than cetuximab in vitro but similar antitumor efficacy as cetuximab in vivo. moreover, ame55 was more efficacious than cetuximab in a lovo cell xenograft tumor model when combined with irinotecan (cpt-11). ame55 concentrates in the mouse xenograft tumor and has less toxicity tha ...201930733972
mammosphere culture of mammary cells from cynomolgus macaques (macaca fascicularis).the mammary gland contains adult stem cells that are capable of self-renewal. although these cells hold an important role in the biology and pathology of the breast, the studies of mammary stem cells are few due to the difficulty of acquiring and expanding undifferentiated adult stem cell populations. in this study, we developed mammosphere cultures from frozen mammary cells of nulliparous cynomolgus macaques (macaca fascicularis) as a culture system to enrich mammary stem cells. small samples o ...201930732675
a comparative study for detecting cyp3a induction by cyp3a probe drugs and endogenous markers in cynomolgus monkeys.cyp3a probe drugs such as midazolam and endogenous markers, and plasma 4β-hydroxycholesterol (4β-ohc) and urinary 6β-hydroxycortisol-to-cortisol ratios (6β-ohc/c) have been used as markers of cyp3a induction in cynomolgus monkeys, as with humans. however, there is limited information on their sensitivity and ability to detect cyp3a induction, as most studies were evaluated only at a high dose of the inducer, rifampicin (rif; 20 mg/kg). in the present study, the cyp3a induction by rif over a rang ...201930724384
cd4cd8 double positive t cell responses during mycobacterium tuberculosis infection in cynomolgus macaques.tuberculosis (tb) kills millions of people every year. cd4 and cd8 t cells are critical in the immune response against tb. t cells expressing both cd4 and cd8 (cd4cd8 t cells) are functionally active and have not been examined in the context of tb.201930723927
pet imaging of dopamine release in the frontal cortex of manganese-exposed non-human primates.humans and non-human primates exposed to excess levels of manganese (mn) exhibit deficits in working memory and attention. frontal cortex and fronto-striatal networks are implicated in working memory and these circuits rely on dopamine for optimal performance. here, we aimed to determine if chronic mn exposure alters in vivo dopamine release (dar) in the frontal cortex of non-human primates. we used [11 c]-flb457 positron emission tomography with amphetamine challenge to measure dar in cynomolgu ...201930720866
intraocular pressure effects and mechanism of action of topical versus sustained-release bimatoprost.to assess the intraocular pressure (iop)-lowering effects of bimatoprost sustained-release implant (bimsr) in normotensive monkeys receiving topical bimatoprost.201930713809
apolipoprotein a-i mimetic peptide l-4f removes bruch's membrane lipids in aged nonhuman primates.multiple evidence lines support bruch's membrane lipid deposition as a major precursor of soft drusen and age-related macular degeneration as including a potentially treatable atherosclerosis-like progression in the subretinal pigment epithelium (rpe)-basal lamina space. we evaluated the effect of anti-inflammatory, antiatherogenic peptide l-4f on bruch's membrane of aged nonhuman primates in a dose-escalating study.201930707219
intrathecal delivery of aav vectors in cynomolgus macaques for cns gene therapy and gene expression analysis in microdissected motor neurons.this protocol describes a method of delivering adeno-associated viral (aav) vectors to the intrathecal space of nonhuman primates for cns-directed gene therapy. it includes the surgical implantation of the catheter, vector infusion, necropsy, laser-capture microdissection of motor neurons, and gene expression analysis. this method allows efficient and reproducible delivery, and would be of interest to test gene therapy vectors for the treatment of disorders of the central nervous system of nonhu ...201930706405
draft genome sequence of atopobacter sp. strain ah10, isolated from a vaginal swab from macaca fascicularis.a bacterial strain belonging to the genus atopobacter was isolated from a vaginal swab from a crab-eating macaque (macaca fascicularis). here, we report the draft genome sequence of this strain, ah10.201930701258
targeting cd74 in multiple myeloma with the novel, site-specific antibody-drug conjugate stro-001.stro-001 is a site-specific, predominantly single-species, fully human, aglycosylated anti-cd74 antibody-drug conjugate incorporating a non-cleavable linker-maytansinoid warhead with a drug-antibody ratio of 2 which was produced by a novel cell-free antibody synthesis platform. we examined the potential pharmacodynamics and anti-tumor effects of stro-001 in multiple myeloma (mm). cd74 expression was assessed in mm cell lines and primary bone marrow (bm) mm biopsies. cd74 mrna was detectable in c ...201830701025
transmission of a novel genotype of hepatitis e virus from bactrian camels to cynomolgus macaques.hepatitis e virus (hev) is zoonotic and a major cause of acute viral hepatitis worldwide. recently, we identified a novel hev genotype 8 (hev8) in bactrian camels in xinjiang, china. however, the epidemiology, pathogenicity, and zoonotic potential of hev8 are unclear. here, we present the prevalence of hev8 in china and investigate its pathogenicity and cross-species transmission in cynomolgus macaques. fresh fecal and milk samples from bactrian camels collected from four provinces/regions in ch ...201930700602
quantitative contrast-enhanced ultrasound of renal perfusion: a technology for the assessment of early diabetic nephropathy in cynomolgus macaques with type 2 diabetes mellitus.the aim of this study was to investigate the effectiveness of contrast-enhanced ultrasound (ceus) in predicting early nephropathy in cynomolgus macaques with spontaneous type 2 diabetes mellitus (t2dm).201930694370
maa868, a novel fxi antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans.a large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. genetic and pharmacologic evidence in humans and animals suggests that reducing factor xi (fxi) levels has the potential to effectively prevent and treat thrombosis with a minimal risk of bleeding. we generated a fully human antibody (maa868) that binds the catalytic domain of both fxi (zymogen) and activated fxi ...201930692123
preclinical modeling of exposure to a global marine bio-contaminant: effects of in utero domoic acid exposure on neonatal behavior and infant memory.domoic acid (da) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. prenatal da exposure occurs through the maternal consumption of contaminated shellfish/finfish. to better understand the fetal risks associated with da, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral da exposure. to this end, 32 adult female macaca fascicularis monkeys were orally dosed wit ...202030690118
intact bioactivities and improved pharmacokinetic of the sl335-ifn-β-1a fusion protein that created by genetic fusion of sl335, a human anti-serum albumin fab, and human interferon-β.recombinant human interferon beta (rifn-β) has long been used as a first-line treatment for multiple sclerosis (ms), and any attempt to develop a long-acting rifn-β is desirable since only one pegylated version of long-acting rifn-β-1a (plegridy) is currently available in clinics. previously, we reported that sl335, a human fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the fcrn recycling mechanism. with the ultimate goal of developing a long-acting ri ...201930684504
multimodal imaging of the retina and choroid in healthy macaca fascicularis at different ages.the aim of this study was to identify the morphological features of the retina and choroid in macaca fascicularis of different ages using multimodal imaging.201930684011
predicting organ carotenoids levels from analysis of plasma could lead to errors: a study in cynomolgus monkeys.carotenoids are phytochemicals with strong antioxidant activity against reactive oxygen species that are widely distributed in fruits and vegetables. the beneficial effects of carotenoids on human health have attracted considerable attention. the plasma carotenoid profile in humans is generally recognized to reflect the dietary carotenoid composition. although carotenoid profile in plasma is believed to correlate well with that in other tissues, the data for tissue accumulation of carotenoids in ...201930683442
the molecular biology and hpv drug responsiveness of cynomolgus macaque papillomaviruses support their use in the development of a relevant in vivo model for antiviral drug testing.due to the extreme tissue and species restriction of the papillomaviruses (pvs), there is a great need for animal models that accurately mimic pv infection in humans for testing therapeutic strategies against human papillomaviruses (hpvs). in this study, we present data that demonstrate that in terms of gene expression during initial viral dna amplification, macaca fascicularis pv (mfpv) types 5 and 8 appear to be similar to mucosal oncogenic hpvs, while mfpv1 (isolated from skin) resembles most ...201930682126
discovery and characterization of potent il-21 neutralizing antibodies via a novel alternating antigen immunization and humanization strategy.interleukin-21 (il-21), a member of the common cytokine receptor γ chain (γc) family, is secreted by cd4+ t cells and natural killer t cells and induces effector function through interactions with the il-21 receptor (il-21r)/γc complex expressed on both immune and non-immune cells. numerous studies suggest that il-21 plays a significant role in autoimmune disorders. therapeutic intervention to disrupt the il-21/il-21r/γc interaction and inhibit subsequent downstream signal transduction could off ...201930682117
steroid-free immune suppression impairs glycemic control in a healthy cynomolgus monkey.the need for chronic immune suppression (is) is one of the hurdles precluding widespread use of islet cell transplantation to restore glycemic control in patients with type 1 diabetes. we report the case of a healthy nonhuman primate (nhp) treated on and off for over 2.5 years with steroid-free is, consisting of daclizumab induction and maintenance therapy with rapamycin and low dose tacrolimus. treatment for 1 year resulted in a striking destabilization of glycemic control, with concomitant dec ...201930675800
in vitro monocyte/macrophage phagocytosis assay for the prediction of drug-induced thrombocytopenia.phagocytosis of platelets by monocytes and macrophages is a primary mechanism of platelet clearance in vivo and has been increasingly implicated in playing an important role in thrombocytopenia mediated by monoclonal antibodies intended for therapeutic purposes. in the present article, we describe an in vitro flow cytometry assay to assess the effect of antibody-mediated platelet phagocytosis by monocytes. freshly isolated platelets were labeled with a fluorescent probe, 5-chloromethylfluorescei ...201930673165
little evidence of zika virus infection in wild long-tailed macaques, peninsular malaysia.we tested a sample of 234 wild long-tailed macaques (macaca fascicularis) trapped in peninsular malaysia in 2009, 2010, and 2016 for zika virus rna and antibodies. none were positive for rna, and only 1.3% were seropositive for neutralizing antibodies. long-tailed macaques are unlikely to be reservoirs for zika virus in malaysia.201930666941
fetoscopic versus ultrasound-guided intravascular delivery of maternal bone marrow cells in fetal macaques: a technical model for intrauterine haemopoietic cell transplantation.significant limitations with existing treatments for major haemoglobinopathies motivate the development of effective intrauterine therapy. we assessed the feasibility of fetoscopic and ultrasound-guided intrauterine haemopoietic cell transplantation (iuhct) in macaque fetuses in early gestation when haemopoietic and immunological ontogeny is anticipated to enable long-term donor cell engraftment.201930661073
homologous recombination-mediated targeted integration in monkey embryos using tale nucleases.non-human primate (nhp) models can closely mimic human physiological functions and are therefore highly valuable in biomedical research. genome editing is now developing rapidly due to the precision and efficiency offered by engineered site-specific endonuclease-based systems, such as transcription activator-like effector nucleases (talens) and the clustered regularly interspaced short palindromic repeats (crispr)/crispr-associated protein-9 nuclease (cas9) system. it has been demonstrated that ...201930646876
histopathological findings in cynomolgus macaques ( macaca fascicularis) consistent with secondary immunological reaction to biotherapeutics with an emphasis on the cns and eye.biotherapeutics are pharmaceutical products derived from or synthesized by biological systems. such molecules carry the potential for immunogenicity which may lead to adverse immune responses. the cynomolgus macaque ( macaca fascicularis) is the species of choice in nonclinical safety assessment of biotherapeutics. the main aim of this study was to confirm whether mononuclear cell infiltrates at specific locations represent a generic effect of biotherapeutics, and therefore the result of their i ...201930636523
both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex.during development of the mammalian cerebral neocortex, postmitotic excitatory neurons migrate toward the outermost region of the neocortex. we previously reported that this outermost region is composed of densely packed relatively immature neurons; we named this region, which is observed during the late stage of mouse neocortical development, the "primitive cortical zone (pcz)." here, we report that postmigratory immature neurons spend about 1-1.5 days in the pcz. an electron microscopic analys ...201930636008
pharmacokinetic properties of arsenic species after intravenous and intragastrical administration of arsenic trioxide solution in cynomolgus macaques using hplc-icp-ms.a rapid and sensitive method was established for arsenic (as) speciation based on high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (hplc-icp-ms). this method was validated for the quantification of four arsenic species, including arsenite (asiii), arsenate (asv), monomethylarsonic acid (mmav) and dimethylarsinic acid (dmav) in cynomolgus macaque plasma. separation was achieved in just 3.7 min with an alkyl reverse phase column and highly aqueous mobi ...201930634677
the immunology of the macaque placenta: a detailed analysis and critical comparison with the human placenta.the cynomolgus monkey is increasingly considered in toxicological research as the most appropriate model for humans due to the species' close physiological contiguity, including reproductive physiology. here, literature on the cynomolgus monkey placenta is reviewed in regards to its similarity to the human placenta and particularly for its immunological role, which is not entirely mirrored in humans. pertinent original data are included in this article. the cynomolgus monkey placenta is evaluate ...201930632863
weekly teriparatide treatment increases vertebral body strength by improving cortical shell architecture in ovariectomized cynomolgus monkeys.weekly teriparatide treatment is reported to reduce the incidence of osteoporotic vertebral fractures. however, the effect of weekly teriparatide on cortical bone has not been clarified. this study aimed to examine the effects of weekly teriparatide treatment on bone mass, intracortical structure, and remodeling of the lumbar vertebral cortical shell and its relation to mechanical properties in ovariectomized cynomolgus monkeys. female monkeys, aged 9 to 15 years, were divided into four groups: ...201930630124
long-tailed macaques (macaca fascicularis) in urban landscapes: gastrointestinal parasitism and barriers for healthy coexistence in northeast thailand.gastrointestinal parasites have diverse life cycles that can involve people, animals, and the environment (e.g., water and soil), demonstrating the utility of one health frameworks in characterizing infection risk. kosumpee forest park (thailand) is home to a dense population of long-tailed macaques (macaca fascicularis) that frequently interact with tourists and local residents. our study investigated the presence of zoonotic parasites, and barriers to healthy coexistence by conducting stool an ...201930628564
genotype 5 hepatitis e virus produced by a reverse genetics system has the potential for zoonotic infection.neither an animal model nor a cell culture system has been established for the genotype 5 hepatitis e virus (g5 hev), and the pathogenicity, epidemiology, and replication mechanism of the virus remain unclear. in this study, we used a reverse genetics system to generate g5 hev and examined the possibility of zoonotic infection. capped and uncapped genomic g5 hev rnas generated by in vitro transcription were transfected into plc/prf/5 cells. infectious g5 hev was recovered from the capped g5 hev ...201930620002
effects of oral domoic acid exposure on maternal reproduction and infant birth characteristics in a preclinical nonhuman primate model.domoic acid (da) is a naturally-occurring excitotoxin, produced by marine algae, which can bioaccumulate in shellfish and finfish. the consumption of seafood contaminated with da is associated with gastrointestinal illness that, in the case of high da exposure, can evolve into a spectrum of responses ranging from agitation to hallucinations, memory loss, seizures and coma. because algal blooms that produce da are becoming more widespread and very little is known about the dangers of chronic, low ...202030615984
administration of recombinant fviia (rfviia) to concizumab-dosed monkeys is safe, and concizumab does not affect the potency of rfviia in hemophilic rabbits.essentials hemophilia patients on concizumab prophylaxis may need rfviia to treat breakthrough bleeds. effect and safety of concizumab + rfviia were tested in vitro and in vivo. concizumab + rfviia had no additive effects on bleeding in hemophilic rabbits. high steady-state levels of concizumab did not affect the safety of rfviia in cynomolgus monkeys. summary: background concizumab is a monoclonal antibody (mab) against tissue factor pathway inhibitor (tfpi), currently in clinical development a ...201930614620
lubricin/proteoglycan 4 detected in vocal folds of humans and five other mammals.lubricin/proteoglycan-4 (prg4) lubricates connective tissues such as joints and tendon sheaths, enabling them to better withstand shearing and frictional forces during motion. we wondered whether prg4 might play a role in phonation, as normal vocal folds withstand repetitive, high-velocity deformations remarkably well. as a first step, we tested whether prg4 is expressed in vocal folds.201930613972
discovery of clinical candidate bms-823778 as an inhibitor of human 11β-hydroxysteroid dehydrogenase type 1 (11β-hsd-1).bms-823778 (2), a 1,2,4-triazolopyridinyl-methanol derived analog, was identified as a potent and selective inhibitor of human 11β-hydroxysteroid dehydrogenase type 1 (11β-hsd-1) enzyme (ic50 = 2.3 nm) with >10,000-fold selectivity over 11β-hsd-2. compound 2 exhibits robust acute pharmacodynamic effects in cynomolgus monkeys (ed50 = 0.6 mg/kg) and in diet-induced obese (dio) mice (ed50 = 34 mg/kg). compound 2 also showed excellent inhibition in an ex vivo adipose dio mouse model (ed50 = 5.2 mg/k ...201830613321
the efficacy of poly-iclc against ebola-zaire virus (ebov) infection in mice and cynomolgus monkeys.the potential protection of poly-iclc (hiltonol®) a double stranded rna (dsrna) against ebov infection was assessed with prophylactic and therapeutic administration to wild type and tlr3-negative mice, and in non-human primates (nhps) by measuring ebol serum titers, survival extension, and serum liver and kidney function markers. various doses of aqueous and liposomal poly-iclc monotherapy provided robust protection in otherwise lethal murine ebov challenge models, when treatment is started on t ...201930611774
effects of fat-to-sugar ratio in excess dietary energy on lipid abnormalities: a 7-month prospective feeding study in adult cynomolgus monkeys.excess energy intake contributes to metabolic disorders. however, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys.201930611256
pain-related behavior and brain activation in cynomolgus macaques with naturally occurring endometriosis.can pain be objectively assessed in macaques with naturally occurring endometriosis?201930597044
the influence of subretinal injection pressure on the microstructure of the monkey retina.to investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model.201830596769
regioselective hydroxylation of an antiarrhythmic drug, propafenone, mediated by rat liver cytochrome p450 2d2 differs from that catalyzed by human p450 2d6.1. propafenone, an antiarrhythmic drug, is a typical human cytochrome p450 (p450) 2d6 substrate used in preclinical studies. here, propafenone oxidation by mammalian liver microsomes was investigated in vitro. 2. liver microsomes from humans and marmosets preferentially mediated propafenone 5-hydroxylation, minipig, rat and mouse livers primarily mediated 4'-hydroxylation, but cynomolgus monkey and dog liver microsomes differently mediated n-despropylation. 3. quinine, ketoconazole or anti-p450 ...201930596462
antibody engineering to generate sky59, a long-acting anti-c5 recycling antibody.modulating the complement system is a promising strategy in drug discovery for disorders with uncontrolled complement activation. although some of these disorders can be effectively treated with an antibody that inhibits complement c5, the high plasma concentration of c5 requires a huge dosage and frequent intravenous administration. moreover, a conventional anti-c5 antibody can cause c5 to accumulate in plasma by reducing c5 clearance when c5 forms an immune complex (ic) with the antibody, whic ...201830592762
metabolic and morphometric changes in indonesian cynomolgus monkeys (macaca fascicularis) fed an atherogenic diet composed of locally sourced ingredients.this study was designed to determine the effects of a new atherogenic diet formulated at institut pertanian bogor (ipb) (bogor, indonesia) on metabolic, morphometric, and carotid artery imaging of cynomolgus monkeys.201830587897
on cute monkeys and repulsive monsters.when i heard that a laboratory in china had cloned two long-tailed macaques, i thought of mary shelley's novel frankenstein. when academics write about the novel, many point out that the reason the creature becomes a "monster" is not that he has any inherently evil qualities but that victor frankenstein, the creature's "mother," immediately rejects him. all later problems can be traced to the fact that frankenstein does not take responsibility for his creation. while i do not disagree with this, ...201830586180
intranodal angiomyomatous hamartoma in a cynomolgus monkey.we describe here an angiomyomatous hamartoma in the right axillary lymph node of a three-year-old male cynomolgus monkey ( macaca fascicularis), used as a control subject in a short-term toxicity study. this is a very rare lesion that has been reported almost exclusively in inguinal lymph nodes, and to date only in human beings. in the present case, light microscopy revealed partial replacement of the lymph node parenchyma by a disorganized, irregular vascular network, sparsely distributed smoot ...201930585127
effects of housing conditions on behaviors and biochemical parameters in juvenile cynomolgus monkeys (macaca fascicularis).to investigate the effects of environmental enrichment on laboratory monkeys, we studied behavioral and physiological differences following changes in housing conditions. ten male and female juvenile cynomolgus monkeys were first housed in pairs for 8 weeks after quarantine/acclimatization (singly housed) and subsequently housed alone for the next 8 weeks. monkeys were subjected to evaluations of body weight gain, stereotypic or affiliative behaviors, cortisol, 4-ethylphenyl sulfate (4eps) and c ...201930584201
rna sequencing of kidney and liver transcriptome obtained from wild cynomolgus macaque (macaca fascicularis) originating from peninsular malaysia.using high-throughput rna sequencing technology, this study aimed to sequence the transcriptome of kidney and liver tissues harvested from peninsular malaysia cynomolgus macaque (macaca fascicularis). m. fascicularis are significant nonhuman primate models in the biomedical field, owing to the macaque's biological similarities with humans. the additional transcriptomic dataset will supplement the previously described peninsular malaysia m. fascicularis transcriptomes obtained in a past endeavour ...201830577850
pharmacokinetics, pharmacodynamics, and safety of e6011, a novel humanized antifractalkine (cx3cl1) monoclonal antibody: a randomized, double-blind, placebo-controlled single-ascending-dose study.e6011 is a novel humanized antifractalkine (fkn) monoclonal antibody being developed as a therapeutic target for crohn's disease, rheumatoid arthritis, and primary biliary cholangitis. this study was a randomized, double-blind, placebo-controlled single-ascending-dose study of intravenous administration of e6011 (0.0006-10 mg/kg) in healthy japanese adult men (n = 64). the starting dose was the minimum anticipated biological effect level (mabel). mabel was estimated by extrapolating results of a ...201930575978
reduced variability in tacrolimus pharmacokinetics following intramuscular injection compared to oral administration in cynomolgus monkeys: investigating optimal dosing regimens.tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. however, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (im) injection and to determine the optimal im dosing regimens in primate models. six male cynomolgus mon ...201930573325
estradiol treatment initiated early after ovariectomy regulates myocardial gene expression and inhibits diastolic dysfunction in female cynomolgus monkeys: potential roles for calcium homeostasis and extracellular matrix remodeling.background left ventricular ( lv ) diastolic dysfunction often precedes heart failure with preserved ejection fraction, the dominant form of heart failure in postmenopausal women. the objective of this study was to determine the effect of oral estradiol treatment initiated early after ovariectomy on lv function and myocardial gene expression in female cynomolgus macaques. methods and results monkeys were ovariectomized and randomized to receive placebo (control) or oral estradiol at a human-equi ...201830571375
cytokine-mediated tissue injury in non-human primate models of viral infections.viral infections trigger robust secretion of interferons and other antiviral cytokines by infected and bystander cells, which in turn can tune the immune response and may lead to viral clearance or immune suppression. however, aberrant or unrestricted cytokine responses can damage host tissues, leading to organ dysfunction, and even death. to understand the cytokine milieu and immune responses in infected host tissues, non-human primate (nhp) models have emerged as important tools. nhp have been ...201830568659
a proof-of-concept evaluation of jtpc and tp-tec as proarrhythmia biomarkers in preclinical species: a retrospective analysis by an hesi-sponsored consortium.based on the ich s7b and e14 guidance documents, qt interval (qtc) is used as the primary in vivo biomarker to assess the risk of drug-induced torsades de pointes (tdp). clinical and nonclinical data suggest that drugs that prolong the corrected qtc with balanced multiple ion channel inhibition (most importantly the l-type calcium, cav1.2, and persistent or late inward sodium current, nav1.5, in addition to human ether-à-go-go-related gene [herg] ikr or kv11.1) may have limited proarrhythmic lia ...201930567462
the feeding ecology and dietary overlap in two sympatric primate species, the long-tailed macaque (macaca fascicularis) and dusky langur (trachypithecus obscurus obscurus), in malaysia.knowledge about the feeding ecology and dietary overlap of sympatric primates is essential for understanding how animals avoid or reduce interspecific competition. from april 2014 to march 2015, we investigated the feeding ecologies of two sympatric primates, a hindgut fermenter, the long-tailed macaque (macaca fascicularis) and a foregut fermenter, the dusky langur (trachypithecus obscurus obscurus), in a mixed landscape consisting of urban and agro-forested areas and forest fragments in malays ...201930564972
once-weekly teriparatide treatment prevents microdamage accumulation in the lumbar vertebral trabecular bone of ovariectomized cynomolgus monkeys.the effect of teriparatide treatment on microdamage accumulation has yet to be examined in animal studies. the purpose of this study was to investigate the effect of once-weekly teriparatide treatment on bone microdamage accumulation and the relationship between microdamage parameters and bone mass, architecture, turnover, and collagen cross-linking in the lumbar vertebral trabecular bone of ovariectomized (ovx) cynomolgus monkeys. female monkeys were divided into four groups (n = 18-20 per grou ...201930564860
variability of spleen and mesenteric lymph node in control cynomolgus monkeys ( macaca fascicularis) from nonclinical safety studies: a retrospective assessment.we assessed the variability of spleen and mesenteric lymph node (mln) microscopic observations and the correlations of these observations with other study data from 478 control cynomolgus monkeys from 53 routine nonclinical safety studies. spleen weight parameters (absolute and relative to body or brain weights) were highly variable both within a control group on an individual study (up to 5.11-fold) and among animals with the same light microscopic observation. grades for microscopic observatio ...201930563426
primate neocortex development and evolution: conserved versus evolved folding.the neocortex, the seat of higher cognitive functions, exhibits a key feature across mammalian species-a highly variable degree of folding. within the neocortex, two distinct subtypes of cortical areas can be distinguished, the isocortex and the proisocortex. here, we have compared specific spatiotemporal aspects of folding between the proisocortex and the isocortex in 13 primates, including human, chimpanzee, and various old world and new world monkeys. we find that folding at the boundaries of ...201930552689
single cell-produced and in vitro-assembled anti-fcrh5/cd3 t-cell dependent bispecific antibodies have similar in vitro and in vivo properties.bispecific antibody production using single host cells has been a new advancement in the antibody engineering field. we previously showed comparable in vitro biological activity and in vivo mouse pharmacokinetics (pk) for two novel single cell variants (v10 and v11) and one traditional dual cell in vitro-assembled anti-human epidermal growth factor receptor 2/cd3 t-cell dependent bispecific (tdb) antibodies. here, we extended our previous work to assess single cell-produced bispecific variants o ...202030550367
anti-tumor effects of mab against l-type amino acid transporter 1 (lat1) bound to human and monkey lat1 with dual avidity modes.l-type amino acid transporter 1 (lat1) disulfide linked to cd98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. in the present study, we developed novel anti-lat1 mabs and showed internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody-dependent cellular cytotoxicity, as well as in vivo antitumor effects in athymic mice. furthermore, we examined the reactivity of mabs with lat1 of macaca fascicularis to evalua ...201930548114
preclinical evaluation of a mage-a3 vaccination utilizing the oncolytic maraba virus currently in first-in-human trials.multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. we evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (nhp) (macaca fascicularis). primates received a replication-deficient adenoviral prime, boosted by the oncolytic maraba mg1 rhabdovirus. both vectors expressed the human mage-a3. no severe adverse events were observed. boosting with m ...201930546947
plasma cholesterol levels in free-ranging macaques compared with captive macaques and humans.plasma total cholesterol in free-ranging japanese macaques (macaca fuscata) on koshima islet and in free-ranging long-tailed macaques (macaca fascicularis) at pangandaran in indonesia was found to occur at very low levels compared with captive macaques and humans. although total cholesterol levels in captive macaques were lower than humans, differences in hdl cholesterol levels were only small. in both sexes of wild and captive japanese macaques, total cholesterol levels decreased from birth thr ...200030545181
diversity of ulbp5 in old-world monkeys (cercopithecidae) and divergence of the ulbp gene family in primates.non-human primates such as rhesus macaque and cynomolgus macaque are important animals for medical research. these species are classified as old-world monkeys (cercopithecidae), in which the immune-related genome structure is characterized by gene duplications. in the present study, we investigated polymorphisms in two genes for ulbp5 encoding ligands for nkg2d. we found 18 and 11 ulbp5.1 alleles and 11 and 13 ulbp5.2 alleles in rhesus macaques and cynomolgus macaques, respectively. in addition, ...201830541969
Displaying items 701 - 800 of 11313