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2019 SPGFZE-PCF Challenge Award

Targeting Tumor-Infiltrating Myeloid Cells for Prostate Cancer Therapy

Principal Investigators: Andrea Alimonti, MD (Institute of Oncology Research), Johann de Bono, MD, PhD (The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust)

Co-Investigators: Arianna Calcinotto, PhD (Institute of Oncology Research), Adam Sharp, MD, PhD (The Institute of Cancer Research and The Royal Marsden Hospital), Antje Neeb, PhD (The Institute of Cancer Research), Bora Gurel, MD (The Institute of Cancer Research), Jon Welti, PhD (The Institute of Cancer Research), Daniela Brina, PhD (Institute of Oncology Research)

Description:

  • Myeloid-derived suppressor cells (MDSCs) are a class of immune cells that infiltrate tumors in large numbers and promote cancer growth. Targeting these cells represents a promising therapeutic approach, however effective treatments remain to be developed.
  • Andrea Alimonti and team have found that MDSCs fuel prostate cancer growth by secreting the protein IL-23. The team will investigate other mechanisms by which MDSCs drive prostate cancer growth and the therapeutic potential for targeting IL-23.
  • To better understand the role of MDSCs in prostate cancer and identify druggable targets, the team will identify proteins that are secreted or present on the surface of MDSCs in prostate tumors.
  • The team will test the impact of targeting these factors in preclinical prostate cancer models and will determine how they impact tumor growth, or if they are associated with specific tumor mutations or patient outcomes.
  • The team will determine if any of the factors secreted by MDSCs can be co-targeted with IL-23 to maximize anti-tumor activity, using preclinical models.
  • The team will initiate a phase 1/2 clinical trial testing the safety and efficacy of the therapeutic anti-IL-23 antibody tildrakizumab in combination with abiraterone in advanced prostate cancer.
  • Correlative studies will be performed using samples from patients on this trial to identify mechanisms of action, potential biomarkers for selecting patients most likely to benefit, and any drug-resistance mechanisms.
  • If successful, this project will lead to an effective new treatment for men with prostate cancer.

What this means to patients: Myeloid-derived suppressor cells (MDSCs) are a class of immune cells which drive prostate cancer growth and represent promising therapeutic targets. Dr. Alimonti and team will determine the mechanisms by which MDSCs drive tumor growth and identify druggable targets. The team will initiate a proof-of-concept clinical trial to test an inhibitor of a major tumor-driving protein secreted by MDSCs, IL-23, which may lead to a new, life-prolonging treatment for patients.