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2024 Larry & Sherry Benaroya – PCF Challenge Award

Development and Optimization of CEACAM5-Targeted Imaging and Therapeutics

Principal Investigators: Scott Tagawa, MD (Weill Cornell Medicine), Sarah Cheal, PhD (Weill Cornell Medicine), Nai-Kong Cheung, MD, PhD (Memorial Sloan Kettering Cancer Center)

Co-Investigators: James Kelly, PhD (Weill Cornell Medicine), David Rickman, PhD (Weill Cornell Medicine), Joseph Osborne, MD, PhD (Weill Cornell Medicine), Edward Fung, PhD (Weill Cornell Medicine), Juan Miguel Mosquera, MD, MSc (Weill Cornell Medicine)

Young Investigator: Sandra Huichochea Castellanos, MD (Weill Cornell Medicine)

Description:

  • Theranostics (therapy + diagnostics) is a precision medicine approach that combines molecular imaging such as PET for a target with a therapeutic radionuclide (radioactive particle) against that same target. Thus, only patients whose tumors sufficiently express the target are given the therapy – a “see what you treat” approach. 
  • PSMA PET + PSMA-targeted radioligand therapy (Pluvicto®) is a prostate cancer theranostic strategy that was approved for advanced metastatic prostate cancer in 2022, but is not curative and not all patients’ tumors express PSMA. The development of theranostics against other prostate cancer targets is highly warranted.
  • Dr. Scott Tagawa and team are developing theranostics against CEACAM5, a protein expressed in some prostate adenocarcinomas, and enriched in advanced prostate tumor types that have lost expression of PSMA.
  • In this project, the team will develop the first CEACAM5-targeted alpha radioligand therapy agent and evaluate potency and safety in preclinical models. Because alpha-emitting radioligands are amongst the most potent payloads, the team will compare direct-CEACAM5 targeted alpha radioligands with a modular approach that first delivers a CEACAM5-targeted antibody to bind to tumor targets, then after excess antibody is cleared from blood, delivers the alpha-emitting radioligand which also binds to the antibody. 
  • The team will also develop a corresponding CEACAM5-PET imaging agent and assess CEACAM5 expression including heterogeneity in the context of therapy.
  • If successful, this project will result in the development of a potent new theranostic for the treatment of patients with highly advanced prostate cancer.

What this means to patients: New treatments are urgently needed for patients with advanced and aggressive forms of prostate cancer. Dr. Tagawa and team are developing a theranostic alpha-emitting targeted radionuclide therapy and PET imaging agent that target CEACAM5, a protein highly expressed on advanced forms of prostate cancer that currently have no effective therapies. This could lead to a potent new precision medicine treatment for these patients.