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Purpose: To detail a technique to implant a double-lumen catheter to remove anti-pig antibodies. We transplanted fetal pig kidneys into cynomolgus monkeys using a double filtration plasma exchange (DFPP) protocol.
Methods: Two approaches for double-lumen catheter insertion in monkeys (3-9.2 kg) were developed. DFPP was performed using hydroxyethyl starch (6%) as a replacement fluid. We transplanted fetal porcine kidneys, administered immunosuppressive agents, and evaluated the grafts.
Results: The catheter insertion site was large, with postoperative hemostasis similar to blind subcutaneous puncture. Monkeys tolerated DFPP well, maintaining stable blood pressure. The technique reduced anti-pig antibodies by 67%, though acute rejection was not fully suppressed.
Conclusion: A safe technique for double-lumen catheter placement in cynomolgus monkeys was developed, along with a DFPP protocol for reducing anti-pig antibodies.
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http://dx.doi.org/10.1590/acb405125 | DOI Listing |
Mol Cancer Ther
September 2025
Novelty Nobility, Seongnam-si, Korea (South), Republic of.
Overexpression and gain-of-function mutations of c-Kit have been implicated in cancers including gastrointestinal stromal tumors (GIST), small cell lung cancer (SCLC), acute myeloid leukemia, and systematic mastocytosis. In clinics, small molecule c-Kit inhibitors often result in secondary c-Kit mutations or are ineffective despite c-Kit overexpression. We developed NN3201, a novel c-Kit targeting antibody-drug conjugate (ADC), via rational design to evaluate its anticancer activity in c-Kit-positive tumors, and preclinical pharmacologic profiles.
View Article and Find Full Text PDFGenome Biol
September 2025
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Background: A growing body of evidence from primate embryos as well as in vitro systems supports the notion that amnion and primordial germ cell (PGC) lineage progressing cells share a common precursor.
Results: To gain comprehensive transcriptomic insights into this critical but poorly understood precursor and its progeny, we examine the evolving transcriptome of a developing human pluripotent stem cell-derived model of amnion and PGC formation at the single cell level. This analysis reveals several continuous amniotic fate progressing states with state-specific markers.
Drug Metab Dispos
August 2025
Department of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, California. Electronic address:
Hydrolases in the eye play an important role in the metabolism of ophthalmic drugs, especially those administered locally to the eyes. With the growing interest in peptide-based therapeutics for treating eye disease, it has become increasingly important to characterize the enzymatic activities of ocular tissues against both small molecules and peptides to better understand their ocular metabolism. In this study, we characterized the activities of hydrolases, including carboxylesterase 1 and 2, arylacetamide deacetylase, paraoxonases, cytidine deaminase, fatty-acid amide hydrolase, and peptidases by incubating probe substrates in whole eye homogenates and vitreous humors from human donors and 3 preclinical species, including New Zealand White rabbits, Gottingen minipigs, and Cynomolgus monkeys.
View Article and Find Full Text PDFBioanalysis
August 2025
Drug Metabolism & Pharmacokinetics (DMPK), Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA.
Background: Drug bridging immunoassays are widely employed as the standard approach for detecting anti-drug antibodies (ADAs) in the development of new biological entities. A major challenge in these assays is mitigating target interference, particularly when the soluble target exists in dimeric forms, which can result in false positive signals and compromise assay specificity.
Research Design And Methods: We developed sensitive and robust ADA assays capable of overcoming target interference to detect antibodies against BI X in both cynomolgus monkey (cyno) plasma and human serum matrices.
J Immunol Methods
August 2025
Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior department of Tuberculosis, the Eighth Medical Center of PLA General Hospital, Beijing 100091, China. Electronic address:
Background: Mycobacterium tuberculosis (MTB) Ag85A has become a component of multiple new tuberculosis vaccines. It is necessary to evaluate the immunogenicity, biological distribution, and safety of ag85a plasmid DNA (pDNA) to lay the foundation for the design of new vaccines.
Method: Chronic toxicity test: cynomolgus monkeys were injected intramuscularly with different doses of ag85a pDNA, and the vaccine absorption kinetics, tissue distribution, and toxicity were observed.