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2025 Michael and Lori Milken Family Foundation – PCF Challenge Award

Theranostic Targeting of a Tumor-Specific Cleaved CDCP1 Epitope in Prostate Cancer

Principal Investigators: Jonathan Chou, MD, PhD (University of California, San Francisco), Jim Wells, PhD (University of California, San Francisco), Michael Evans, PhD (University of California, San Francisco), Rahul Aggarwal, MD (University of California, San Francisco), Joshua Lang, MD (University of Wisconsin)

Co-Investigator: Kevin Leung, PhD (University of California, San Francisco)

Young Investigators: Carissa Chu, MD (University of California, San Francisco), Apurva Pandey, PhD (University of California, San Francisco)

Description:

  • Prostate cancer is one of the most common cancers in men, and new treatments are urgently needed, especially for advanced disease that no longer responds to current therapies. Many modern treatments work by recognizing specific proteins on the surface of cancer cells (for example, PSMA), but these proteins are often also found on normal cells, which can lead to harmful side effects.
  • Dr. Jonathan Chou and team have discovered a unique form of a protein called CDCP1 CDCP1 (also known as CUB domain containing protein 1) that appears only on prostate cancer cells. This form is created when enzymes in the tumor environment “cut” the protein in a specific way, revealing a new surface target that healthy cells do not have.
  • The team has developed unique antibody binders that specifically recognize this cancer-specific version of CDCP1. In this project, the team will re-engineer these CDCP1-binders into multiple therapeutic formats, including radiotherapies, T-cell engagers, chimeric antigen receptor (CAR) T cells, and evaluate their anti-tumor efficacy, safety and specificity across relevant prostate cancer models.
  • They will also characterize levels of cancer-specific-CDCP1 in prostate cancer samples, and develop new imaging tests to detect cancer-specific-CDCP1 in tumors and in cancer cells circulating in the blood.
  • If successful, this project will develop a safer and more effective combined diagnosis and therapy strategy (“theranostics”) ready for clinical trials in patients with prostate cancer.

What this means to patients: While many treatment options exist for advanced prostate cancer, none are curative and many have side effects due to targeting proteins that are also present in normal cells. Dr. Chou and team have identified a form of the CDCP1 protein only expressed in prostate cancer cells and will develop new cancer-specific-CDCP1 treatments and imaging agents that are ready for testing in clinical trials. This could lead to a new highly targeted treatment approach for patients with prostate cancer, that is designed to seek out and destroy tumor cells and spare normal tissues.