> Our Work > The Work We Fund

2022 John Tyson – PCF Young Investigator Award

Bispecific Immunotherapy Strategies to Overcome the Immunosuppressive Prostate Tumor Microenvironment

Bilal A. Siddiqui, MD
The University of Texas MD Anderson Cancer Center

Mentors: Christopher Logothethis, MD, Sumit Subudhi, MD, PhD

Description:

  • Prostate cancer has a highly immunosuppressive tumor microenvironment, which has contributed to poor responses to immunotherapies. This appears particularly true with checkpoint immunotherapy treatment in patients with bone-predominant metastatic disease, the most common site of metastasis in prostate cancer.
  • Bispecific immunotherapies simultaneously bind to tumor and immune cells, to bring immune cells directly into contact with tumor cells and kill them. Studies suggest that bispecifics may be able to better promote immune cell infiltration into the prostate bone tumor microenvironment, compared with checkpoint immunotherapies.
  • Dr. Bilal Siddiqui is investigating the mechanisms of response and resistance to bispecific immunotherapies in prostate cancer.
  • In this project, Dr. Siddiqui and team will determine immune cell types and locations within the tumor microenvironment that are associated with response to bispecifics versus checkpoint immunotherapies in patients with advanced prostate cancer.
  • Mechanisms of resistance to treatment with bispecifics versus checkpoint immunotherapies in patients with advanced prostate cancer will be identified.
  • Co-clinical studies will be performed to validate mechanisms of resistance in bone vs. soft tissue sites of prostate cancer metastases and identify possible new treatment combinations that can overcome immunotherapy resistance.
  • If successful, this project will identify mechanisms and biomarkers of response and resistance to bispecific immunotherapies in metastatic prostate cancer and identify possible new rational treatment combinations.

What this means to patients: Immunotherapy can be a powerful form of cancer treatment but has yet to be optimized in prostate cancer. Dr. Siddiqui will identify mechanisms of response to bispecific immunotherapies in metastatic prostate cancer. This will enable the identification of rational combination approaches to improve clinical outcomes in patients with metastatic prostate cancer.