James R Cockey, Gavin M Zhou, Emily N Kulp, Christian A Urbina, Christina Kerkenpaß, Cynthia A Leifer
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引用次数: 0
Abstract
Objective: The purpose of this study was to develop procedures to engineer feline chimeric antigen receptor (CAR) T cells.
Methods: 6 healthy cats were used in this study. Blood was collected, and CD3+ primary T cells were enriched by magnetic activated cell sorting, expanded, and used to generate CAR T cells.
Results: Phorbol myristate acetate plus ionomycin and concanavalin A induced similar early proliferation of CD3-enriched feline CD4+ and CD8+ T cells but phorbol myristate acetate plus ionomycin induced greater expansion over 12 days. Chimeric antigen receptor T cells were engineered by transduction with an FIV-based lentiviral system to express a human CD19 CAR. Feline CD19 CAR T cells demonstrated specific cytotoxicity against human CD19+ target cells. Conditions were developed to polarize the T cells to THelper subsets.
Conclusions: We generated functional and specific primary feline CAR T cells and demonstrated conditions to polarize the cells, which may be therapeutically advantageous for CAR T-cell use in a variety of disease contexts.
Clinical relevance: CAR T therapy has been used with great success for human hematologic malignancies and is under development for use in canines. Our study is the first demonstration of functional feline CAR T cells and describes the procedures for their engineering. These findings lay the foundation for future development of CAR T therapy for multiple feline diseases.
期刊介绍：
The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.
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