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2025 Estate of Frederick Belli and Estate of Joseph Schenick – PCF Young Investigator Award

Investigating a Novel Immunotherapeutic Targeting CEACAM5 in Androgen Indifferent Prostate Cancer

Charles Nguyen, MD
City of Hope

Mentors: Tanya Dorff; John Shively; Jeffrey Wong

Description:

  • Metastatic castration-resistant prostate cancer (mCRPC) remains incurable, particularly in patients with aggressive subtypes that have lost typical prostate cell features, including neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC). These subsets have limited treatment options and poor prognoses, highlighting the urgent need for novel therapeutic strategies.
  • CEACAM5, a cell surface marker enriched in NEPC and DNPC, has been identified as a potential target for immunotherapy. Dr. Charles Nguyen hypothesizes that a novel CEACAM5-targeted immunotherapy (CEA-ICK) can induce antitumor activity by enhancing immune cell signaling and increasing immune cell infiltration of these aggressive tumor types.
  • Dr. Nguyen has initiated a phase 1 clinical trial testing CEA-ICK in combination with stereotactic body radiation therapy (SBRT) in patients with CEACAM5-positive advanced solid tumors, including NEPC and DNPC prostate cancer.
  • In this project, Dr. Nguyen will leverage patient samples from this ongoing trial to investigate the tumor-immune microenvironment in CEACAM5-positive prostate cancer patients treated with CEA-ICK. He will also test the performance of a novel CEACAM5-targeted PET imaging agent in identifying patients most likely to benefit from CEA-ICK therapy.
  • If successful, this project will lead to a new immunotherapy-based treatment and companion PET diagnostic for patients with the most lethal forms of prostate cancer. 

What this means to patients: mCRPC remains incurable and new treatments are urgently needed. Dr. Nguyen’s project will investigate a new CEACAM5-targeted immunotherapy for various types of mCRPC, as well as a PET imaging agent to identify which patients have tumors that express CEACAM5 and may benefit from this treatment. This will provide mechanistic and early efficacy data to support future phase 2 trials and broader efforts to optimize immunotherapies for patients with advanced, aggressive prostate cancer.