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2021 J. Eustace Wolfington-PCF Young Investigator Award

Impact of the Microbiome on PSCA-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy for Prostate Cancer

John P. Murad, PhD
City of Hope

Mentor: Saul Priceman, PhD

Description:

  • Chimeric antigen receptor (CAR) T cells are a type of immunotherapy where a patients’ own T cells are engineered to target and kill their cancer. CARs targeting a number of cancer antigens, including the prostate stem cell antigen (PSCA), are under development for the treatment of prostate and other cancers. A clinical trial testing the safety and efficacy of PSCA-targeted CAR T cells in prostate cancer is ongoing at The City of Hope.
  • The microbiome is the complex community of microbes that live on the skin and mucosal surfaces of the human body. The microbiome regulates many normal body functions, including immune education. Further, the composition of the microbiome has been shown to influence responses to cancer therapies, including immunotherapy.
  • Dr. John Murad is studying if the microbiome influences treatment responses to CAR T cells, in an attempt to identify strategies to improve the efficacy of CARs to target immunosuppressive solid tumors, such as prostate cancer.
  • In this project, Dr. Murad will evaluate the impact of microbiome manipulation on systemic immunity, the tumor microenvironment, and the efficacy of PSCA-CAR T cell therapy in animal models of prostate cancer.
  • The microbiome of human prostate cancer patients enrolled in the ongoing PSCA-CAR T cell clinical trial will be characterized, and whether microbiome status correlates with response and/or resistance to therapy will be determined.
  • If successful, this project will characterize the role of the microbiome in responses to PSCA-CAR T cell immunotherapy and inform the next stages of clinical development of prostate cancer targeted cell therapy.

What this means to patients: CAR T cells are a promising class of experimental treatments for prostate cancer that are currently being tested in clinical trials. Dr. Murad is evaluating the role of the host microbiome in influencing responses to CAR T cells. This will improve our understanding of the role of microbiome in therapeutic responses, and ultimately provide avenues to improve clinical outcomes of prostate cancer patients undergoing CAR T cell immunotherapy.