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2021 Pfizer-PCF Young Investigator Award

Identifying and Targeting Immunogenic Prostate Cancer

David Einstein, MD
Harvard: Beth Israel Deaconess Medical Center

Mentors: Steven Balk, MD, PhD, Kai Wucherpfennig, MD, PhD

Description:

  • Prostate cancer is typically considered a poorly immunogenic tumor, meaning anti-tumor immune responses that develop are weak and/or rare, which has limited the efficacy of immunotherapies.
  • Dr. Einstein and colleagues have observed a subset of primary prostate cancers which appear to be highly immunogenic, characterized by high levels of tumor-infiltrating T cells and expression of the immunotherapy target PD-L1. A clinical trial is underway to test the efficacy of anti-PD1 immunotherapy in patients whose primary tumors have these features and are experiencing a PSA recurrence after primary therapy.
  • In this project, Dr. Einstein will develop biomarkers to identify immunogenic primary prostate tumors, as these are most likely to respond to immunotherapies.
  • The team will identify at least 100 cases of immunogenic primary prostate cancer, including patients from the trial, and new cases identified from archival samples and from patients who have just undergone prostatectomy. Patients of African ancestry (AA) will enriched for, to ensure generalizability and because a particularly immunogenic phenotype has been described in association with AA.
  • Studies will be performed to comprehensively characterize the numbers, types, and functions of immune cells infiltrating these tumors.
  • Whether any specific tumor mutations are associated with immunogenic prostate cancer will be investigated. The impact of RB1, BRCA2, and CHD1 mutations on anti-tumor immune responses will be specifically evaluated, as these mutations are hypothesized to increase tumor immunogenicity.
  • If successful, this project will define immune and genomic mechanisms and biomarkers of immunogenic prostate cancer. These biomarkers can be used to select patients which may be more responsive to immunotherapies.

What this means to patients: Dr. Einstein is identifying and characterizing a subset of aggressive localized prostate cancer that generates anti-tumor immune responses. This will enable the development new immunotherapy approaches to target these tumors in neo-adjuvant and other settings.