Publications

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distinct spatiotemporal mechanisms underlie extra-classical receptive field modulation in macaque v1 microcircuits.complex scene perception depends upon the interaction between signals from the classical receptive field (crf) and the extra-classical receptive field (ecrf) in primary visual cortex (v1) neurons. although much is known about v1 ecrf properties, we do not yet know how the underlying mechanisms map onto the cortical microcircuit. we probed the spatio-temporal dynamics of ecrf modulation using a reverse correlation paradigm, and found three principal ecrf mechanisms: tuned-facilitation, untuned-su ...202032458798
development of cdx-527: a bispecific antibody combining pd-1 blockade and cd27 costimulation for cancer immunotherapy.cd27 is a costimulatory molecule that provides a complementary target to the pd-1/pd-l1 checkpoint axis on t cells. combining a cd27 agonist antibody with pd-1/pd-l1 blockade has shown synergistic antitumor activity in preclinical models, which led to clinical studies of the combination in cancer patients. we theorized that coupling cd27 costimulation with pd-1/pd-l1 blockade in a bispecific antibody (bsab) may provide greater immune activating properties than combining the individual mabs due t ...202032451681
expression of cannabinoid cb1 r-gpr55 heteromers in neuronal subtypes of the macaca fascicularis striatum.the cannabinoid cb1 receptor (cb1 r) is the most abundant g protein-coupled receptor in the central nervous system, consistent with the important role of endocannabinoids as neuromodulators. cannabinoids also modulate the function of g protein-coupled receptor 55 (gpr55), which forms heteroreceptor complexes with the cb1 r in the striatum. the aim was to characterize cannabinoid cb1 r-gpr55 heteromers (cb1 r/gpr55hets) in the basal ganglia input nuclei of nonhuman primates, macaca fascicularis, ...202032594556
the relative efficacy of the cranium and os coxa for taxonomic assessment in macaques.the cranium is generally considered more reliable than the postcranium for assessing primate taxonomy, although recent research suggests that pelvic shape may be equally reliable. however, little research has focused on intrageneric taxonomic discrimination. here, we test the relative taxonomic efficacy of the cranium and os coxa for differentiating two macaque species, with and without considering sexual dimorphism.202032594518
nonclinical safety assessment of amg 553, an investigational chimeric antigen receptor t-cell therapy for the treatment of acute myeloid leukemia.feline mcdonough sarcoma-like tyrosine kinase 3 (flt3), a tyrosine-protein kinase involved in hematopoiesis, is detectable on the cell surface of approximately 80% of leukemia isolates from adult patients with acute myeloid leukemia (aml). amg 553 is an investigational chimeric antigen receptor (car) t-cell immunotherapy for the treatment of aml. flt3 expression analysis and in vitro and in vivo studies were leveraged to evaluate the nonclinical safety of amg 553. cynomolgus monkeys administered ...202032589753
applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.alphaviruses such as venezuelan equine encephalitis virus (veev) and eastern equine encephalitis virus (eeev) are arboviruses that can cause severe zoonotic disease in humans. both veev and eeev are highly infectious when aerosolized and can be used as biological weapons. vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. the cynomolgus macaque (macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or ...202032584818
raav8 and raav9-mediated long-term muscle transduction with tacrolimus (fk506) in non-human primates.to establish an efficient, safe immunosuppressive regimen of adeno-associated vector (aav)-mediated gene therapy for duchenne muscular dystrophy (dmd), we evaluated the effect of tacrolimus (fk506) on skeletal muscle transduction with aav8 and aav9 vectors expressing the lacz and microdystrophin (m3) genes labeled by flag. we utilized 3- to 4-year-old macaca fascicularis, screened for neutralizing antibodies against aav. 3 days before aav injection and throughout the experiment, 0.06 mg/kg tacro ...202032577431
natural history of aerosol induced lassa fever in non‑human primates.lassa virus (lasv), an arenavirus causing lassa fever, is endemic to west africa with up to 300,000 cases and between 5000 and 10,000 deaths per year. rarely seen in the united states, lassa virus is a cdc category a biological agent inasmuch deliberate aerosol exposure can have high mortality rates compared to naturally acquired infection. with the need for an animal model, specific countermeasures remain elusive as there is no fda-approved vaccine. this natural history of aerosolized lassa vir ...202032485952
anti-vascular endothelial growth factor antibody limits vascular leakage and decreases subretinal fibrosis in a cynomolgus monkey choroidal neovascularization model.this study was conducted to evaluate the effects of anti-vascular endothelial growth factor (vegf) antibody (bevacizumab) on vascular leakage and fibrosis in a monkey choroidal neovascularization (cnv) model. the relationship between fibrotic tissue and subretinal hyper-reflective material (shrm) in optical coherence tomography (oct) images was also investigated.202032445455
characterization of tumour-infiltrating lymphocytes in a tumour rejection cynomolgus macaque model.immunotherapy has emerged as a promising and effective treatment for cancer, yet the clinical benefit is still variable, in part due to insufficient accumulation of immune effector cells in the tumour microenvironment. better understanding of tumour-infiltrating lymphocytes (tils) from nonhuman primate tumours could provide insights into improving effector cell accumulation in tumour tissues during immunotherapy. here, we characterize tils in a cynomolgus macaque tumour model in which the tumour ...202032439888
assessment of parp-1 distribution in tissues of cynomolgus monkeys.the poly(adp-ribose) polymerase 1 (parp-1) enzyme has received much attention in the last decade due to its promising role in cancer therapeutics. despite the expanding use of parp inhibitors in cancer therapy, little is known about parp-1 tissue distribution. our study provides a detailed survey of parp-1 tissue and cellular distribution using well-preserved cynomolgus monkey organs and a well-characterized, highly specific monoclonal parp-1 antibody. overall, parp-1 was detected in most organs ...202032436762
correlations of serum biochemistry profile with ultrasonic histogram of liver, gallbladder, and kidneys and morphometry of rescued long-tailed macaques (macaca fascicularis).serum biochemistry and ultrasonography can be useful diagnostic tools in evaluating the general health condition of long-tailed macaques in rescue and rehabilitation centers.202032463113
sedative and physiological effects of alfaxalone intramuscular administration in cynomolgus monkeys (macaca fascicularis).to evaluate the sedative and physiological effects of alfaxalone intramuscular (im) administration, 12 healthy cynomolgus monkeys were administered single im doses of alfaxalone at 0.625 mg/kg (alfx0.625), 1.25 mg/kg (alfx1.25), 2.5 mg/kg (alfx2.5), 5 mg/kg (alfx5), 7.5 mg/kg (alfx7.5), or 10 mg/kg (alfx10); saline was used as the control (cont). the sedative effects were subjectively evaluated using a composite measure scoring system in six animals. changes in respiratory rate, pulse rate, non- ...202032461537
mait cells are functionally impaired in a mauritian cynomolgus macaque model of siv and mtb co-infection.mucosal-associated invariant t (mait) cells can recognize and respond to some bacterially infected cells. several in vitro and in vivo models of mycobacterium tuberculosis (mtb) infection suggest that mait cells can contribute to control of mtb, but these studies are often cross-sectional and use peripheral blood cells. whether mait cells are recruited to mtb-affected granulomas and lymph nodes (lns) during early mtb infection and what purpose they might serve there is less well understood. furt ...202032433713
toward a macaque model of hiv-1 infection: roadblocks, progress, and future strategies.the human-specific tropism of human immunodeficiency virus type 1 (hiv-1) has complicated the development of a macaque model of hiv-1 infection/aids that is suitable for preclinical evaluation of vaccines and novel treatment strategies. several innate retroviral restriction factors, such as apobec3 family of proteins, trim5α, bst2, and samhd1, that prevent hiv-1 replication have been identified in macaque cells. accessory proteins expressed by simian immunodeficiency virus (siv) such as viral in ...202032477302
generation of cynomolgus monkey fetuses with intracytoplasmic sperm injection based on the mii-stage oocytes acquired by personalized superovulation protocol.mature oocytes at the metaphase ii status (mii-stage oocytes) played an important role in assisted reproductive technology in non-human primates.202032476321
everestmab, a novel long-acting glp-1/anti glp-1r nanobody fusion protein, exerts potent anti-diabetic effects.in the present study, a novel single domain antibody (sdab) fusion protein, named everestmab, composing of a mutated glp-1(a8g) fused to the tandem bispecific humanized glp-1r-targeting and albumin-binding nanobodies was designed and characterized for the therapies for type 2 diabetes mellitus (t2dm). surface plasmon resonance (spr) measurements demonstrated everestmab associates with serum albumins of rat and monkey species with high affinity, and tends to be cross-reactive with rat and monkey ...202032468873
cs1003, a novel human and mouse cross-reactive pd-1 monoclonal antibody for cancer therapy.the programmed cell death protein 1 (pd-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. pd-1 antibodies can block the interaction of pd-1 with its ligands (pd-l1 and pd-l2), restore t cells activation, and elicit antitumor activity. in this paper, we reported a novel pd-1 monoclonal antibody (mab) cs1003, which is a humanized igg4 pd-1 mab generated by conventional hybridoma technology, and current ...202032467569
in vitro and in vivo interspecies chimera assay using early pig embryos.chimeric pigs harboring organs derived from human stem cells are promising for patient-specific regenerative therapies. induced pluripotent stem cells (ipscs) can contribute to all cell types of the fetus, including germline after injection into embryos. however, ethical concerns prohibit testing human ipscs in chimera assays. here, we evaluated porcine embryos as hosts for an interspecies chimera assay using ipscs from either cynomolgus monkeys (cyipscs) or mouse (mipscs). to establish an in vi ...202032429746
a non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs.stroke is a devastating disease. endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. in this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. ...202032428423
method development and validation of lc-ms/ms-based assay for the simultaneous quantitation of trastuzumab and pertuzumab in cynomolgus monkey serum and its application in pharmacokinetic study.we present a simple and robust lc-ms/ms assay for the simultaneous quantitation of an antibody cocktail of trastuzumab and pertuzumab in monkey serum. the lc-ms/ms method saved costs, decreased the analysis time, and reduced quantitative times relative to the traditional ligand-binding assays. the serum samples were digested with trypsin at 50°c for 60 min after methanol precipitation, ammonium bicarbonate denaturation, dithiothreitol reduction, and iodoacetamide alkylation. the tryptic peptides ...202032428305
sars-cov-2 causes covid-19-like disease in cynomolgus macaques. 202032424314
discovery of indoximod prodrugs and characterization of clinical candidate nlg802.a series of different prodrugs of indoximod, including estesrs and peptide amides were synthesized with the aim of improving its oral bioavailability in humans. the pharmacokinetics of prodrugs that were stable in buffers, plasma and simulated gastric and intestinal fluids was first assessed in rats after oral dosing in solution or in capsule formulation. two prodrugs that produced the highest exposure to indoximod in rats were further tested in cynomolgus monkeys, a species in which indoximod h ...202032422549
cholecystokinin-1 receptor agonist induced pathological findings in the exocrine pancreas of non-human primates.cholecystokinin (cck) may potentially be used to treat obesity. however, it is well-known to induce acute pancreatitis and pancreas neoplasia in rodents, but not in primates. here we report the nonclinical safety profile of a long-acting cck-1 receptor (cck-1r) agonist, nn9056, in rats and monkeys to support a first-in-man clinical trial with nn9056.202032422327
a strategy for personalized treatment of ips-retinal immune rejections assessed in cynomolgus monkey models.recently, we successfully transplanted an autograft, or major histocompatibility complex (mhc)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (ipsc-rpe) cells in patients with age-related macular degeneration. however, there was an issue regarding immune rejection after transplantation. in this study, we established a preoperational in vitro "drug-lymphocytes-grafts immune reaction (drug-lgir)" test to determine the medication for immune rejection using ...202032349277
cell atlas of aqueous humor outflow pathways in eyes of humans and four model species provides insight into glaucoma pathogenesis.increased intraocular pressure (iop) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering iop is the only proven treatment strategy to delay disease progression. the main determinant of iop is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous iop elevations. drainage occurs through two pathways in the anterior segment of the ...202032341164
genetic variants of n-acetyltransferases 1 and 2 (nat1 and nat2) in cynomolgus and rhesus macaques.in humans, polymorphic n-acetyltransferases nat1 and nat2 are important enzymes that metabolize endogenous and exogenous compounds, including drugs. these enzymes exhibit considerable inter-individual variability in humans. the cynomolgus macaque is a nonhuman primate species that is widely used in drug metabolism studies. nat1/2 in these macaques have molecular and enzymatic similarities to their human orthologs; however, genetic polymorphisms in nat1/2 have not been fully investigated in this ...202032339492
recombination between high-risk human papillomaviruses and non-human primate papillomaviruses: evidence of ancient host switching among alphapapillomaviruses.we use all the currently known 405 papillomavirus (pv) sequences, 343 curated pv sequences from both humans and animals from the pave data base, to analyse the recombination dynamics of these viruses at the whole genome levels. after showing some evidence of human and non-human primate pv recombination, we report a comprehensive recombination analysis of all currently known 82 alphapapillomaviruses (alpha-pvs). we carried out an exploratory study and found novel recombination events between high ...202032385625
inhibition of complement pathway activation with pozelimab, a fully human antibody to complement component c5.complement is a key component of the innate immune system. inappropriate complement activation underlies the pathophysiology of a variety of diseases. complement component 5 (c5) is a validated therapeutic target for complement-mediated diseases, but the development of new therapeutics has been limited by a paucity of preclinical models to evaluate the pharmacokinetic (pk) and pharmacodynamic (pd) properties of candidate therapies. the present report describes a novel humanized c5 mouse and its ...202032384086
liver extracellular volume fraction values obtained with magnetic resonance imaging can quantitatively stage liver fibrosis: a validation study in monkeys with nonalcoholic steatohepatitis.this study was to evaluate the diagnostic value of liver extracellular volume (lecv) for the staging of liver fibrosis in a cynomolgus monkey model of nonalcoholic steatohepatitis (nash).202032377814
in vitro screening and transfection concentration optimization of cynomolgus monkey iκbα-sirna.to seek for a small interfering rna (sirna) sequence targeting a cynomolgus monkey inhibitor of nuclear factor kappa b α (iκbα) that can specifically and effectively suppress iκbα gene expression of cynomolgus monkey ciliary muscle (cm) cells and trabecular meshwork (tm) cells in vitro and screen for optimal sirna transfection concentration.202032377413
the gut microbiome modulates gut-brain axis glycerophospholipid metabolism in a region-specific manner in a nonhuman primate model of depression.emerging research demonstrates that microbiota-gut-brain (mgb) axis changes are associated with depression onset, but the mechanisms underlying this observation remain largely unknown. the gut microbiome of nonhuman primates is highly similar to that of humans, and some subordinate monkeys naturally display depressive-like behaviors, making them an ideal model for studying these phenomena. here, we characterized microbial composition and function, and gut-brain metabolic signatures, in female cy ...202032376998
design and characterization of novel oxyntomodulin derivatives with potent dual glp-1/glucagon receptor activation and prolonged antidiabetic effects.to investigate the combination of dimerization and pegylation to enhance the receptor activation and in vivo stability of oxyntomodulin (oxm).202032304764
comparative pathogenesis of covid-19, mers, and sars in a nonhuman primate model.the current pandemic coronavirus, severe acute respiratory syndrome-coronavirus 2 (sars-cov-2), was recently identified in patients with an acute respiratory syndrome, coronavirus disease 2019 (covid-19). to compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with sars-cov-2 or middle east respiratory syndrome (mers)-cov and compared the pathology and virology with historical reports of sars-cov infections. in sars-cov-2-infected macaques, v ...202032303590
comparison of the inducibility of cyp mrna exposed to typical inducers in fresh and cryopreserved cynomolgus monkey hepatocytes.herein, we evaluated cyps and their nuclear receptor mrna induction by exposure to typical inducers, omeprazole, rifampicin, and phenobarbital in cynomolgus monkey hepatocytes. six freshly-isolated hepatocytes and 6 cryopreserved hepatocytes from cynomolgus monkey liver were prepared for a 14-day monolayer culture, 28-day co-culture with feeder cells, and 28-day 3d spheroid culture with feeder cells. omeprazole and rifampicin respectively induced cyp1a1 and cyp3a8 mrnas, while phenobarbital indu ...202032303457
efficacy of neuraminidase inhibitors against h5n6 highly pathogenic avian influenza virus in a nonhuman primate model.attention has been paid to h5n6 highly pathogenic avian influenza virus (hpaiv) because of its heavy burden on the poultry industry and human mortality. since an influenza a virus carrying n6 neuraminidase (na) has never spread in humans, the potential for h5n6 hpaiv to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. we used nonhuman primates to elucidate the pathogenesis of h5n6 hpaiv as well as to determine the efficacy of antiviral d ...202032284377
a single lentivector dna based immunization contains a late heterologous sivmac251 mucosal challenge infection.variety of conventional vaccine strategies tested against hiv-1 have failed to induce protection against hiv acquisition or durable control of viremia. therefore, innovative strategies that can induce long lasting protective immunity against hiv chronic infection are needed. recently, we developed an integration-defective hiv lentidna vaccine that undergoes a single cycle of replication in target cells in which most viral antigens are produced. a single immunization with such lentidna induced lo ...202032278522
potent and rapid reversal of the von willebrand factor inhibitor aptamer bt200.bt200, a pegylated form of the aptamer bt100, inhibits binding of von willebrand factor (vwf) to platelet glycoprotein gpib, preventing arterial thrombosis in cynomolgus monkeys. it is being developed for secondary prevention of arterial thrombosis such as stroke or myocardial infarction. inhibition of thrombogenesis by bt200 is expected to provide a therapeutic benefit. however, there may be unexpected bleeding (eg, incidental trauma) in which a reversal agent is required. to address this need, ...202032275107
fviii half-life extension by coadministration of a d'd3 albumin fusion protein in mice, rabbits, rats, and monkeys.a novel mechanism for extending the circulatory half-life of coagulation factor viii (fviii) has been established and evaluated preclinically. the fviii binding domain of von willebrand factor (d'd3) fused to human albumin (rd'd3-fp) dose dependently improved pharmacokinetics parameters of coadministered fviii in all animal species tested, from mouse to cynomolgus monkey, after iv injection. at higher doses, the half-life of recombinant fviii (rviii-singlechain) was calculated to be increased 2. ...202032374879
identification and classification of interstitial cells in the mouse renal pelvis.platelet-derived growth factor receptor-α (pdgfrα) is a novel biomarker along with smooth myosin heavy chain for the pacemaker cells (previously termed 'atypical' smooth muscle cells) in the murine and cynomolgus monkey pelvis-kidney junction. pdgfrα+ cells present in adventitial and urothelial layers of murine renal pelvis do not express smooth muscle myosin heavy chain (smmhc) but are in close apposition to nerve fibres. most c-kit+ cells in the renal pelvis are mast cells. mast cells (cd117+ ...202032415739
pet imaging of [11c]mpc-6827, a microtubule-based radiotracer in non-human primate brains.dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and alzheimer's disease. imaging of microtubules in vivo using positron emission tomography (pet) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. we developed [11c]mpc-6827, the first brain-penetrating pet radiotracer to image microtubules in vivo in the mouse brain. the aim of the pres ...202032414052
a single-cell transcriptomic landscape of primate arterial aging.our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. here we report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. gene network analyses characterize transcriptional landmarks that regulate vascula ...202032371953
maternal-fetal disposition of domoic acid following repeated oral dosing during pregnancy in nonhuman primate.domoic acid (da) is a marine algal toxin that causes acute and chronic neurotoxicity in animals and humans. prenatal exposure to da has been associated with neuronal damage and cognitive and behavioral deficits in juvenile california sea lions, cynomolgus monkeys and rodents. yet, the toxicokinetics (tk) of da during pregnancy and the maternal-fetal disposition of da have not been fully elucidated. in this study, we investigated the tk before, during, and after pregnancy and the maternal-fetal d ...202032360744
tissue cross-reactivity studies of cpgj701 in humans, cynomolgus monkeys and sprague-dawley rats and correlation analysis with in vivo toxicity.cpgj701 is a recombinant humanized anti-human epidermal growth factor receptor-2 (her2) monoclonal antibody-derivative of the cytotoxic agent maytansine (dm1) conjugate for the treatment of her2-positive metastatic breast cancer. tissue cross-reactivity (tcr) studies of cpgj701 in a complete panel of normal human, cynomolgus monkey and sprague-dawley were performed to provide evidence for selecting animal species for use in preclinical toxicity studies and predicting primary target organs and cl ...202032355769
anatomical study of the incisivus labii superioris and inferioris muscles in non-human primates.the facial muscles have significant roles for vocalization, feeding, and facial expression in both human and non-human primates. of these, the anatomy of the incisivus labii superioris (ils) and incisivus labii inferioris (ili), which are considered as the accessory bundle of the orbicularis oris (oo) in humans, has rarely been documented in the literature. our current understanding of the function of the ils and ili is that they probably retract the upper and lower lips. also, there is no accou ...202032420698
inferring functional patterns of tool use behavior from the temporal structure of object play sequences in a non-human primate species.inferring functional components of behavioral sequences is a crucial but challenging task. a systematic comparison of their temporal structure is a good starting point, based on the postulate that more functional traits are less structurally variable. we studied stone handling behavior (sh) in balinese long-tailed macaques, a versatile form of stone-directed play. we tested the hypothesis that stones are used by male monkeys to stimulate their genitals in a sexual context (i.e., "sex toy" hypoth ...202032417233
positron emission tomography imaging evaluation of a novel 18f-labeled sigma-1 receptor radioligand in cynomolgus monkeys.we report a convenient radiosynthesis and the first positron emission tomography (pet) imaging evaluation of [18f]fbfp as a potent sigma-1 (σ1) receptor radioligand with advantageous characteristics. [18f]fbfp was synthesized in one step from an iodonium ylide precursor. in cynomolgus monkeys, [18f]fbfp displayed high brain uptake and suitable tissue kinetics for quantitative analysis. it exhibited heterogeneous distribution with higher regional volume of distribution (vt) values in the amygdala ...202032356969
intra-csf aav9 and aavrh10 administration in nonhuman primates: promising routes and vectors for which neurological diseases?the identification of the most efficient method for whole central nervous system targeting that is translatable to humans and the safest route of adeno-associated virus (aav) administration is a major concern for future applications in clinics. additionally, as many aav serotypes were identified for gene introduction into the brain and the spinal cord, another key to human gene-therapy success is to determine the most efficient serotype. in this study, we compared lumbar intrathecal administrati ...202032355866
anatomy of the dura mater venous sinus of alouatta belzebul.the anatomy of the dura mater's venous sinuses is important in the veterinary clinical and surgical area, for cranial procedures and interventions of wild animals, in addition to assisting in the management of neurological diseases, which can prevent serious complications. the macroscopic anatomy of the venous sinuses of the dura mater of alouatta belzebul was studied. five adult specimens, males and females, were dissected and fixed in 10% formaldehyde solution. in the dura mater of the alouatt ...202032738181
comparison of nonhuman primates identified the suitable model for covid-19.identification of a suitable nonhuman primate (nhp) model of covid-19 remains challenging. here, we characterized severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in three nhp species: old world monkeys macaca mulatta (m. mulatta) and macaca fascicularis (m. fascicularis) and new world monkey callithrix jacchus (c. jacchus). infected m. mulatta and m. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. viral genomes wer ...202032814760
non-human primate determinants of natural killer cells in tissues at steady-state and during simian immunodeficiency virus infection.natural killer (nk) cells play essential roles in immunity to viruses and tumors. their function is genetically determined but also modulated by environmental factors. the distribution and functional regulation of these cells vary depending on the tissue. nk cell behavior in lymphoid tissues is so far understudied. non-human primate (nhp) models are essential for the development of therapies and vaccines against human diseases, and access to nhp tissues allows insights into spatial regulations o ...202033013901
immune profiling of influenza-specific b- and t-cell responses in macaques using flow cytometry-based assays.influenza remains a significant global public health burden, despite substantial annual vaccination efforts against circulating virus strains. as a result, novel vaccine approaches are needed to generate long-lasting and universal broadly cross-reactive immunity against distinct influenza virus strains and subtypes. several new vaccine candidates are currently under development and/or in clinical trials. the successful development of new vaccines requires testing in animal models, other than mic ...202032741011
differences in frontal network anatomy across primate species.the frontal lobe is central to distinctive aspects of human cognition and behavior. some comparative studies link this to a larger frontal cortex and even larger frontal white matter in humans compared with other primates, yet others dispute these findings. the discrepancies between studies could be explained by limitations of the methods used to quantify volume differences across species, especially when applied to white matter connections. in this study, we used a novel tractography approach t ...202031949106
predicted structural differences of four fertility-related y-chromosome proteins in macaca mulatta, m. fascicularis, and their indochinese hybrids.species in the genus macaca typically live in multimale-multifemale social groups with male macaques exhibiting some of the largest testis:body weight ratios among primates. males are believed to experience intense levels of sperm competition. several spermatogenesis genes are located on the y-chromosome and, interestingly, occasional hybridization between two species has led to the introgression of the rhesus macaque (macaca mulatta) y-chromosome deep into the range of the long-tailed macaque ( ...202033146441
recombinant slamblind measles virus is a promising candidate for nectin-4-positive triple negative breast cancer therapy.one of the most refractory breast cancer types is triple negative (tn) breast cancer, in which cells are resistant to both hormone and herceptin treatments and, thus, often cause recurrence and metastasis. effective treatments are needed to treat tn breast cancer. we previously demonstrated that rmv-slamblind, a recombinant measles virus, showed anti-tumor activity against breast cancer cells. here, we examined whether rmv-slamblind is effective for treating tn breast cancer. nectin-4, a recepto ...202033145396
three decades of philippine nonhuman primate studies: research gaps and opportunities for philippine primatology.the philippines is considered a megadiverse country. however, there are few published studies on its nonhuman primate (nhp) species (carlito syrichta, macaca fascicularis, and nycticebus menagensis). understanding the nature and extent of existing nhp research in the philippines would help us to determine research gaps and opportunities. thus, studies on nhps of philippine origin were retrieved from online databases including google scholar, researchgate, primate lit, the integrated taxonomic in ...202032681352
plasma and hepatic concentrations of acetaminophen and its primary conjugates after oral administrations determined in experimental animals and humans and extrapolated by pharmacokinetic modeling.plasma concentrations of acetaminophen, its glucuronide and sulfate conjugates, and cysteinyl acetaminophen were experimentally determined after oral administrations of 10 mg/kg in humanized-liver mice, control mice, rats, common marmosets, cynomolgus monkeys, and minipigs; the results were compared with reported human pharmacokinetic data. among the animals tested, only rats predominantly converted acetaminophen to sulfate conjugates, rather than glucuronide conjugates. in contrast, the values ...202033179995
expression of functional sulfotransferases (sult) 1a1, 1a3, 1b1, 1c2, 1e1, and 2a1 in common marmosets.cytosolic sulfotransferases (sults), which mediate the conjugation of drugs with 3'-phosphoadenosine-5'-phosphosulfate, have been characterized in humans and cynomolgus monkeys. however, sults remain to be evaluated in common marmosets, a species of non-human primate often employed in drug metabolism and pharmacokinetic studies of endogenous and exogenous compounds. in this study, marmoset sult1a1, 1a3, 1b1, 1c2, 1e1, and 2a1 cdnas were isolated and characterized, based on genome data. the deduc ...202032768400
non-human primate models of dengue virus infection: a comparison of viremia levels and antibody responses during primary and secondary infection among old world and new world monkeys.due to the global burden of dengue disease, a vaccine is urgently needed. one of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. preclinical studies in vaccine development usually include parameters such as safety evaluation, ...202032230836
cd8 t cells show protection against highly pathogenic simian immunodeficiency virus (siv) after vaccination with siv gene-expressing bcg prime and vaccinia virus/sendai virus vector boosts.toward development of a dual vaccine for human immunodeficiency virus (hiv)-1 and tuberculosis infections, we developed a urease-deficient bacillus calmette-guérin (bcg) strain tokyo172 (bcgδurease) to enhance its immunogenicity. bcgδurease expressing simian immunodeficiency virus (siv) gag induced bcg antigen-specific cd4+ and cd8+ t cells more efficiently, and more gag-specific cd8+ t cells. we evaluated its protective efficacy against siv infection in cynomolgus monkeys of asian origin, shown ...202033087465
a novel fusion of il-10 engineered to traffic across intestinal epithelium to treat colitis.il-10 is a potent anti-inflammatory cytokine capable of suppressing a number of proinflammatory signals associated with intestinal inflammatory diseases, such as ulcerative colitis and crohn's disease. clinical use of human il-10 (hil-10) has been limited by anemia and thrombocytopenia following systemic injection, side effects that might be eliminated by a gut-restricted distribution. we have identified a transcytosis pathway used by cholix, an exotoxin secreted by nonpandemic forms of the inte ...202033148717
development of highly optimized antibody-drug conjugates (adc) against cd33 and cd123 for acute myeloid leukemia.mortality due to acute myeloid leukemia (aml) remains high, and the management of relapsed or refractory aml continues to be therapeutically challenging. the reapproval of mylotarg, an anti-cd33-calicheamicin antibody-drug conjugate (adc), has provided a proof-of-concept for an adc-based therapeutic for aml. several other adcs have since entered clinical development of aml but have met with limited success. we sought to develop a next-generation adc for aml with a wide therapeutic index that ove ...202033148666
a novel dopamine d3r agonist sk609 with norepinephrine transporter inhibition promotes improvement in cognitive task performance in rodent and non-human primate models of parkinson's disease.mild cognitive impairment is present in a number of neurodegenerative disorders including parkinson's disease (pd). mild cognitive impairment in pd (pd-mci) often manifests as deficits in executive functioning, attention, and spatial and working memory. clinical studies have suggested that the development of mild cognitive impairment may be an early symptom of pd and may even precede the onset of motor impairment by several years. dysfunction in several neurotransmitter systems, including dopami ...202033141071
factors influencing taxonomic unevenness in scientific research: a mixed-methods case study of non-human primate genomic sequence data generation.scholars have noted major disparities in the extent of scientific research conducted among taxonomic groups. such trends may cascade if future scientists gravitate towards study species with more data and resources already available. as new technologies emerge, do research studies employing these technologies continue these disparities? here, using non-human primates as a case study, we identified disparities in massively parallel genomic sequencing data and conducted interviews with scientists ...202033047065
preclinical activity of sar408701: a novel anti-ceacam5-maytansinoid antibody-drug conjugate for the treatment of ceacam5-positive epithelial tumors.carcinoembryonic antigen-related cell adhesion molecule 5 (ceacam5) is a glycoprotein that has limited expression in normal adult tissues, but is overexpressed in carcinomas of the gastrointestinal tract, the genitourinary and respiratory systems, and breast cancer. as such, ceacam5 is an attractive target for antibody-based therapies designed to selectively deliver cytotoxic drugs to certain epithelial tumors. here, we describe preclinical data for a novel antibody-drug conjugate (adc), sar4087 ...202033046521
antibody-mediated activation of the fgfr1/klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans.fibroblast growth factor 21 (fgf21) controls metabolic organ homeostasis and eating/drinking behavior via fgf receptor 1/klothoβ (fgfr1/klb) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. chronic administration of recombinant fgf21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. here we show that the bispecific anti-fgfr1/klb agonist ...202033139537
nvx-cov2373 vaccine protects cynomolgus macaque upper and lower airways against sars-cov-2 challenge.there is an urgent need for a safe and protective vaccine to control the global spread of sars-cov-2 and prevent covid-19. here, we report the immunogenicity and protective efficacy of a sars-cov-2 subunit vaccine (nvx-cov2373) produced from the full-length sars-cov-2 spike (s) glycoprotein stabilized in the prefusion conformation. cynomolgus macaques (macaca fascicularis) immunized with nvx-cov2373 and the saponin-based matrix-m™ adjuvant induced anti-s antibody that was neutralizing and blocke ...202033139139
central nervous system migration of astaxanthin and adonixanthin following their oral administration in cynomolgus monkeys.astaxanthin, which has been shown to have significant antioxidant activity, is rapidly spreading as a health functioning ingredient in the health food and cosmetics sectors worldwide. it is well known that astaxanthin acts on the brain; however, there is little evidence of brain translocation due to the difficulty in identifying astaxanthin in tissues. therefore, in this study, we investigated the concentrations of astaxanthin and adonixanthin, the latter being a biosynthetic intermediate from β ...202033132354
genome editing of ccr5 by crispr-cas9 in mauritian cynomolgus macaque embryos.the discovery that ccr5 serves as an r5-hiv-1 co-receptor, coupled with findings of protection from hiv infection in individuals lacking ccr5, led to the exploration of novel therapeutic strategies for hiv infection based on genome editing of ccr5. advancing translation of ccr5-mutant-based cellular therapies for hiv requires development of novel physiologically relevant animal models. mauritian cynomolgus macaques (mcms), with high degree of mhc allele sharing, are valuable models for hiv-1 res ...202033116147
transplantation of t-cell receptor α/β-depleted allogeneic bone marrow in nonhuman primates.allogeneic hematopoietic stem cell transplantation (allohsct) is a potentially curative treatment for hematologic cancers and chronic infections such as human immunodeficiency virus (hiv). its success in these settings is attributed to the ability of engrafting immune cells to eliminate cancer cells or deplete the hiv reservoir (graft-versus-host effect [gvhe]). however, allohsct is commonly associated with graft-versus-host diseases (gvhds) causing significant morbidity and mortality, thereby r ...202033176119
pet/ct imaging of 89zr-n-sucdf-pembrolizumab in healthy cynomolgus monkeys.programmed cell death-1 receptor (pd-1) and its ligand (pd-l1) are the targets for immunotherapy in many cancer types. although pd-1 blockade has therapeutic effects, the efficacy differs between patients. factors contributing to this variability are pd-l1 expression levels and immune cells present in tumors. however, it is not well understood how pd-1 expression in the tumor microenvironment impacts immunotherapy response. thus, imaging of pd-1-expressing immune cells is of interest. this study ...202033104972
vaccination with intradermal bacillus calmette-guérin provides robust protection against extrapulmonary tuberculosis but not pulmonary infection in cynomolgus macaques.recently, the efficacy of mycobacterium bovis bacillus calmette-guérin (bcg) vaccination is being reassessed in accordance with the achievements of clinical tuberculosis (tb) vaccine research. however, the mechanisms ultimately determining the success or failure of bcg vaccination to prevent pulmonary tb remain poorly understood. in this study, we analyzed the protective effects of intradermal bcg vaccination by using specific pathogen-free cynomolgus macaques of asian origin that were intraderm ...202033097574
nonclinical safety, tolerance and pharmacodynamics evaluation for meplazumab treating chloroquine-resistant plasmodium falciparum.meplazumab is an anti-cd147 humanized igg2 antibody. the purpose of this study was to characterize the nonclinical safety, tolerance and efficacy evaluation of meplazumab treating chloroquine resistant plasmodium falciparum. meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys. no observed adverse effect level was 12 mg/kg. no difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab. no increased levels o ...202033088688
dualseqdb: the host-pathogen dual rna sequencing database for infection processes.despite antibiotic resistance being a matter of growing concern worldwide, the bacterial mechanisms of pathogenesis remain underexplored, restraining our ability to develop new antimicrobials. the rise of high-throughput sequencing technology has made available a massive amount of transcriptomic data that could help elucidate the mechanisms underlying bacterial infection. here, we introduce the dualseqdb database, a resource that helps the identification of gene transcriptional changes in both p ...202033084904
novel lcat (lecithin:cholesterol acyltransferase) activator ds-8190a prevents the progression of plaque accumulation in atherosclerosis models.enhancement of lcat (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. to evaluate this concept, we characterized our novel, orally administered, small-molecule lcat activator ds-8190a, which was created from high-throughput screening and subsequent derivatization. we also focused on its mechanism of lcat activation and the therapeutic activity with improvement of hdl (high-density lipoprotein) functionality. approach and results: ds-8190a activ ...202033086872
interleukin-1β and tumor necrosis factor-α affect cytochrome p450 expression in cynomolgus macaque hepatocytes.the cynomolgus macaque, partly due to its evolutionary closeness to humans, is an important nonhuman primate species used in drug metabolism studies. in humans, expressions of cytochromes p450 (p450s), including the important drug-metabolizing enzyme p450 3a4, are affected by various cytokines. however, this phenomenon has not been fully investigated in cynomolgus macaques. in this study, the effects of cytokines on p450 expression were investigated using the quantitative polymerase chain reacti ...202032253084
multilocus sequence typing of enterocytozoon bieneusi in crab-eating macaques (macaca fascicularis) in hainan, china.enterocytozoon bieneusi is one of common intestinal pathogens in humans and animals including non-human primates (nhps). many zoonotic pathogens including e. bieneusi have been found in these animals. however, there are few studies on the population structure of e. bieneusi in nhps. to infer the gene diversity and population genetics of e. bieneusi, we selected 88 e. bieneusi-positive samples from crab-eating macaques for multilocus characterizations in this study.202032268912
group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (macaca fascicularis).enhanced pre- and postnatal development (eppnd) studies have become the default developmental toxicity test for biopharmaceuticals if nonhuman primates represent the relevant species. spontaneous pregnancy losses and infant deaths can be significant in macaques such as long-tailed macaques. the international council for harmonisation of technical requirements for pharmaceuticals for human use (ich) guideline s6(r1) states that pregnancy outcome can be judged also by the normogram-based variabili ...202032232119
the effects of b1344, a novel fibroblast growth factor 21 analog, on nonalcoholic steatohepatitis in nonhuman primates.nonalcoholic steatohepatitis has emerged as a major cause of liver diseases with no effective therapies. here, we evaluate the efficacies and pharmacokinetics of b1344, a long-acting polyethylene glycolylated (pegylated) fibroblast growth factor 21 analog, in a nongenetically modified nonhuman primate species that underwent liver biopsy and demonstrate the potential for efficacies in humans. b1344 is sufficient to selectively activate signaling from the βklotho/fgfr1c receptor complex. in cynomo ...202032354858
comprehensive analysis of cardiac function, blood biomarkers and histopathology for milrinone-induced cardiotoxicity in cynomolgus monkeys.the objective of this study was to elucidate the underlying cardiotoxic mechanism of milrinone, a camp phosphodiesterase 3 inhibitor, by evaluating cardiac functions, blood biomarkers including cardiac troponin i (ctni), micrornas (mir-1, mir-133a and mir-499a) and various endogenous metabolites, and histopathology in conscious cynomolgus monkeys. milrinone at doses of 0, 3 and 30 mg/kg were orally administered to monkeys (n = 3-4/group), and the endpoints were evaluated 1 to 24 h post-dosing. m ...202032353509
prolonged intraocular residence and retinal tissue distribution of a fourth-generation compstatin-based c3 inhibitor in non-human primates.age-related macular degeneration (amd) is a leading cause of irreversible vision loss among the elderly population. genetic studies in susceptible individuals have linked this ocular disease to deregulated complement activity that culminates in increased c3 turnover, retinal inflammation and photoreceptor loss. therapeutic targeting of c3 has therefore emerged as a promising strategy for broadly intercepting the detrimental proinflammatory consequences of complement activation in the retinal tis ...202032229292
toward development of the delayed tolerance induction protocol for vascularized composite allografts in nonhuman primates.transplantation of vascularized composite allografts is limited mainly by the need for life-long immunosuppression. the consequent side effects and looming specter of chronic rejection portend eventual allograft loss. development of tolerogenic protocols is thus of utmost importance to the field of vascularized composite allograft transplantation.202032221215
rhesus macaques are most likely the ancestral source of helicobacter suis infection in pigs and not cynomolgus macaques. 202032219893
local immunosuppression for vascularized composite allografts: application of topical fk506-tyrospheres in a non-human primate model.transplantation of vascularized composite allografts (vcas) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. while short- to intermediate-term vca survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. topical immunosuppression is ...202032352521
identification and analysis of components in yizhi granule and cynomolgus monkey plasma after oral administration by uplc/esi-q-tof ms and their protective effects on pc12 cells.yizhi granule (yzg) is a health food containing six traditional chinese medicines (tcms). it improves memory barriers in rat experiments. here, we describe the first fast and sensitive ultraperformance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (uplc/esi-q-tof ms) method for analyzing yzg in plasma. we used this technique for studies in cynomolgus monkey plasma. by comparing retention time, ms, and ms/ms data of reference compounds, 70 compounds wer ...202032351755
immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against ccl20 is associated with complement-containing drug aggregates.despite the potential for the chemokine class as therapeutic targets in immune mediated disease, success has been limited. many chemokines can bind to multiple receptors and many receptors have multiple ligands, with few exceptions. one of those exceptions is ccl20, which exclusively pairs to ccr6 and is associated with several immunologic conditions, thus providing a promising therapeutic target. following successful evaluation in a single dose, first time in human clinical study, gsk3050002-a ...202032325480
prima subretinal wireless photovoltaic microchip implantation in non-human primate and feline models.to evaluate the surgical technique for subretinal implantation of two sizes of prima photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials.202032267845
quantitative magnetic susceptibility assessed by 7t magnetic resonance imaging in alzheimer's disease caused by streptozotocin administration.streptozotocin treatment has emerged as an alternative model of sporadic alzheimer's disease (sad). streptozotocin-induced alterations in iron and calcium levels reflect magnetic susceptibility changes, while susceptibility distribution in the cerebral regions has not been reported yet. this study aimed to investigate susceptibility distribution in the limbic system after streptozotocin administration to cynomolgus monkeys for exploring informative sad biomarkers. quantitative susceptibility map ...202032269937
divergent strategies in faeces avoidance between two cercopithecoid primates.parasites constitute a major selective pressure which has shaped animal behaviour through evolutionary time. one adaption to parasites consists of recognizing and avoiding substrates or cues that indicate their presence. among substrates harbouring infectious agents, faeces are known to elicit avoidance behaviour in numerous animal species. however, the function and mechanisms of faeces avoidance in non-human primates has been largely overlooked by scientists. in this study, we used an experimen ...202032269806
enhanced normograms and pregnancy outcome analysis in nonhuman primate developmental toxicity studies.the incidence of spontaneous pregnancy/infant losses is highly variable in long-tailed macaques (cynomolgus monkey), making it potentially difficult to ascertain test item-related effects in developmental toxicity studies. therefore, pregnancy normograms had been developed by jarvis et al. [1] to aid in the distinction of normal (e.g. test facility background) versus non-normal pregnancy outcomes. these normograms were mostly derived from embryo-fetal development studies and from ppnd studies wi ...202032413491
preclinical characterization of an antibody-drug conjugate targeting cs-1 and the identification of uncharacterized populations of cs-1-positive cells.multiple myeloma is a hematologic cancer that disrupts normal bone marrow function and has multiple lines of therapeutic options, but is incurable as patients ultimately relapse. we developed a novel antibody-drug conjugate (adc) targeting cs-1, a protein that is highly expressed on multiple myeloma tumor cells. the anti-cs-1 mab specifically bound to cells expressing cs-1 and, when conjugated to a cytotoxic pyrrolobenzodiazepine payload, reduced the viability of multiple myeloma cell lines in v ...202032404408
potential use of actigraphy to measure sleep in monkeys: comparison with behavioral analysis from videography.sleep is indispensable for human health, with sleep disorders initiating a cascade of negative consequences. as our closest phylogenetic relatives, non-human primates (nhps) are invaluable for comparative sleep studies and exhibit tremendous potential for improving our understanding of human sleep and related disorders. previous work on measuring sleep in nhps has mostly used electroencephalography or videography. in this study, simultaneous videography and actigraphy were applied to observe sle ...202032400976
multiplex precise base editing in cynomolgus monkeys.common polygenic diseases result from compounded risk contributed by multiple genetic variants, meaning that simultaneous correction or introduction of single nucleotide variants is required for disease modeling and gene therapy. here, we show precise, efficient, and simultaneous multiplex base editing of up to three target sites across 11 genes/loci in cynomolgus monkey embryos using crispr-based cytidine- and adenine-base editors. unbiased whole genome sequencing demonstrates high specificity ...202032393762
novel mono-pegylated dimeric glp-1 conjugate with enhanced receptor activation and prolonged anti-diabetes efficacies.to design and evaluate novel mono-pegylated dimeric glp-1 conjugate with enhanced glp-1 receptor activation and prolonged anti-diabetes efficacies.202032387412
first radiolabeling of a ganglioside with a positron emitting radionuclide: in vivo pet demonstrates low exposure of radiofluorinated gm1 in non-human primate brain.gangliosides are biologically important glycolipids widely distributed in vertebrate cells. an important member of the ganglioside family is the monosialylganglioside gm1, which has been suggested as a potential therapeutic for parkinson's disease. in the current study, a late-stage radiofluorination protocol was developed, in which fluorine-18 was introduced by substitution of a terminal tosyl group in the fatty acid backbone of gm1. the radiofluorination procedure was remarkably simple and fur ...202032324990
establishment of macaque trophoblast stem cell lines derived from cynomolgus monkey blastocysts.the placenta forms a maternal-fetal junction that supports many physiological functions such as the supply of nutrition and exchange of gases and wastes. establishing an in vitro culture model of human and non-human primate trophoblast stem/progenitor cells is important for investigating the process of early placental development and trophoblast differentiation. in this study, we have established five trophoblast stem cell (tsc) lines from cynomolgus monkey blastocysts, named mactsc #1-5. fibrob ...202032321940
induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin.streptozotocin (stz)- induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs. there are serious side effects of this method, including nausea, emesis, weight loss, liver damage, renal failure, and metabolic acidosis. in order to reduce the side effects, diabetic monkeys were induced using clinical-grade stz. however, clinical-grade stz is not available in china. here, we establised a method ...202032318663
barusiban, a selective oxytocin receptor antagonist: placental transfer in rabbit, monkey, and human†.the use of drugs in pregnancy always raises concerns regarding potential fetal exposure and possible adverse effects through their accumulation in fetal tissues and organs. barusiban is an oxytocin antagonist under development for potential use as tocolytic in preterm-labor patients. it displays greater affinity for the oxytocin receptor compared to vasopressin v1a receptor and would thus not interfere with vasopressin-induced effects of the v1a receptor. barusiban placental transfer was determi ...202032307542
low replicative fitness of neuraminidase inhibitor-resistant h7n9 avian influenza a virus with r292k substitution in neuraminidase in cynomolgus macaques compared with i222t substitution.human cases of h7n9 influenza a virus infection have been increasing since 2013. the first choice of treatment for influenza is neuraminidase (na) inhibitors (nais), but there is a concern that nai-resistant viruses are selected in the presence of nais. in our previous study, an h7n9 virus carrying aa substitution of threonine (t) for isoleucine (i) at residue 222 in na (na222t, n2 numbering) and an h7n9 virus carrying aa substitution of lysine (k) for arginine (r) at residue 292 in na (na292k, ...202032272175
target arm affinities determine preclinical efficacy and safety of anti-her2/cd3 bispecific antibody.systemic cytokine release and on-target/off-tumor toxicity to normal tissues are the main adverse effects limiting the clinical utility of t cell-redirecting therapies. this study was designed to determine how binding affinity for cd3 and tumor target her2 impact the efficacy and nonclinical safety of anti-her2/cd3 t cell-dependent antibodies (tdbs). affinity was found to be a major determinant for the overall tolerability. higher affinity for cd3 associated with rapidly elevated peripheral cyto ...202032271166
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