Targeting the Cell Surfaceome of Aggressive Neuroendocrine Prostate Cancer
Abstract
In this reporting period, we developed an in vitro method to reprogram prostate adenocarcinoma to neuroendocrine prostate cancer (NEPC) which has enabled unprecedented functional characterization of candidate factors involved in NE transdifferentiation. We also expanded our characterization of CEACAM5 expression in lethal metastatic castration-resistant prostate cancer relative to other cell surface antigens under clinical investigation. We redirected the CEACAM5 antibody-drug conjugate labetuzumab govitecan originally developed for colorectal cancer to prostate cancer and demonstrate striking antitumor activity across multiple preclinical models of CEACAM5 NEPC. Ongoing studies with an L1CAM CE7 chimeric antigen receptor also indicate antigen-specific T cell activation and cytotoxicity against NEPC cell lines. Lastly, we have started to evaluate six fully humanized L1CAM CE7 candidate antibodies for specific binding to the tumor-selective, glycosylated CE7 epitope.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2020
- Accession Number
- AD1108794
Entities
People
- John K Lee
Organizations
- Fred Hutchinson Cancer Center