Canine CAR T Cell Therapy for Solid Tumors
Abstract
Adoptive cell transfer of chimeric antigen receptors (CAR) T cells has successfully targeted hematological malignancies in human patients. However, unpredicted side effects experienced after injection of the CAR T cells suggests the need for an optimal predictive preclinical animal model. Dogs have intact immune systems and develop solid tumors spontaneously with similar morphology and genetics to humans. I hypothesize that generating CAR T cells for dogs will closely mimic human patients' outcomes, thus providing new understandings of the safety of this immunotherapy. In addition to the dog as a preclinical model, we propose using a universal CAR T cell to overcome various tumor-related immunosuppressive challenges and control the killing of the target cells. To achieve this, we established methods for activating and expanding canine T cells to a clinically relevant scale. Then, we expressed a second-generation anti-FITC-8-41BB-ζ CAR T cell via lentiviral transduction. In the presence of the correct low-molecular-weight bispecific adapter, we showed in-vitro CAR-mediated function. Our results proved that it is feasible to generate functional canine anti-FITC-8-BB-ζ CAR T cells for therapy.
Degree
M.S.
Advisors
Mohammed, Purdue University.
Subject Area
Biomedical engineering|Oncology|Immunology|Pharmacology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.