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2022 William C. and Gina B. Carithers – PCF Young Investigator Award

Multiplex Engineered CAR iNK Cells Targeting B7-H3 to Treat Metastatic Castration Resistant Prostate Cancers

Nicholas Zorko, MD, PhD
University of Minnesota / Masonic Cancer Center

Mentors: Jeffrey Miller, MD, Emmanuel Antonarakis, MD, Martin Felices, PhD

Description:

  • Immunotherapies have provided significant clinical benefit to patients with many types of metastatic cancers, but have yet to be optimized in prostate cancer. This is because prostate cancer is typically immunologically “cold,” due to an immune-suppressive tumor microenvironment (TME).
  • NK cells are immune cells with potent tumor cell-killing capabilities. Engineered NK cells (iNK) that recognize and target tumor-associated proteins, are a new type of treatment being investigated.
  • Dr. Nicholas Zorko is developing iNK cells that can target the B7-H3 protein. B7-H3 is highly expressed on CRPC but not on normal tissues, making it a promising target for immune-based therapies in patients with prostate cancer.
  • In this project, Dr. Zorko and team will develop B7-H3-targeting human iNK cells and investigate their efficacy and functional mechanisms in preclinical CRPC models.
  • Whether the anti-tumor efficacy of B7-H3-targeting iNK cells is enhanced when combined with PSMA or PD-L1-targeting antibodies will be investigated.
  • In addition, whether the efficacy of B7-H3-targeting iNK cells is enhanced in combination with antibodies blocking the effects of the immune-suppressive protein TGF-beta, will be studied.
  • If successful, this project will provide the basis for clinical trials evaluating the safety and tolerability of CAR iNK in patients with refractory metastatic CRPC, who currently have few effective options to control disease progression.

What this means to patients: New immunotherapy approaches are urgently needed for patients with prostate cancer. Dr. Zorko and team are developing a novel immunotherapy, in which NK cells are engineered to target the prostate tumor protein B7-H3. This project will determine mechanisms of action and provide preclinical rationale for testing this treatment in clinical trials.