UC San Diego

ABSTRACT OF THE THESIS

Antitumor Activity of Chimeric Antigen T-cells Developed from Anti-ROR1 Monoclonal Antibody in Prostate Cancer Models

by

Jamillah H Murtadha

Master of Science in Biological SciencesUniversity of California San Diego, 2022 Dr. Christina Jamieson, Chair Professor Maho Niwa, Co-Chair

Prostate Cancer (PCa) is the second leading cause of cancer death in men, and there is no cure. The current treatments, such as Androgen Deprivation Therapy (ADT), cause adverse effects. ADT can be initially effective. However, PCa in most patients on ADT is eventually determined to be castration-resistant. Therefore, new therapies and treatments are needed. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is involved in embryogenesis. However, some findings correlate ROR1 with many cancers, including bone metastatic castrate-resistant PCa (CRPC) (Zhao et al., 2021)). Rather than using an anti-androgen drug to target CRPC, the drug therapy of interest is a biologic generated from chimeric antigen receptor (CAR) T-cells which targets the extracellular domain of ROR1 that has been derived from the monoclonal antibody, Cirmtuzumab. This study aims to determine the effects of anti-ROR1 CAR-T cells derived from Cirmtuzumab on prostate cancer tumors developed from PC3, a common prostate cancer cell line. For 145 days, we monitored the tumors of mice inoculated with anti-ROR1 CAR T-cells with an in-vivo bioluminescence imaging system assay, IVIS. By day 29, we observed 4 out of 9 mice had complete tumor regression. In conclusion, CAR T-cell treated mice with complete tumor regression had a longer survival rate of 145 days vs. 42 days for the control group animals. In conclusion, this pre-clinical study showed the efficacy of the Cirmtuzumab Anti-ROR1 CART against a human neuroendocrine prostate cancer tumor xenograft model in mice and supported additional studies on the path leading to human clinical trials.