Race-related Differences in Sipuleucel-T Response Among Men with Metastatic Castrate-Resistant Prostate Cancer.

Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored.

Patients' blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers pre- and post-treatment. Baseline cumulative product parameters (total nucleated and CD54+ cell counts, and CD54 upregulation) were evaluated. IgM titers against the immunogen PA2024, the target antigen PAP, prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) were quantified by ELISA. Cytotoxic T lymphocyte activity was determined by ELISpots, and cytokine and chemokine concentrations by Luminex.

Twenty-nine African Americans (AA) and 28 non-African Americans (non-AA) with mCRPC received sipuleucel-T. Baseline total nucleated cell count, CD54+ cell count, CD54 expression, and cumulative product parameters were higher in non-AA. Although PSA baseline levels were higher in AA, there were no racial differences in IgM antibody and IFN- ELISpots responses against PA2024, PAP, PSA and PSMA pre- and post-treatment. Expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells, and the levels of Th1 cytokine granulocyte-macrophage colony-stimulating factor and chemokines CCL4 and CCL5, were significantly higher in AA pre- and/or post-treatment. Despite no difference in the overall survival, PSA changes from baseline were significantly different between the two races.

The data suggest that immune correlates in blood differ in AA and non-AA with mCRPC pre- and post-sipuleucel-T.

Cancer research communications. 2024 Jun 10 [Epub ahead of print]

Elisabeth I Heath, Archana Thakur, Wei Chen, Clara Hwang, Channing J Paller, Frank C Cackowski, Julie L Boerner, Lance Heilbrun, Melanie P Smith, Dana L Schalk, Amy Schienschang, Sarah A Whitaker, Amanda Polend, Daryn Smith, Ulka N Vaishampayan, Brenda Dickow, Lawrence G Lum

Karmanos Cancer Center, Detroit, MI, United States., University of Virginia Cancer Center, Charlottesville, VA, United States., Wayne State University, Detroit, MI, United States., Henry Ford Health System, Detroit, MI, United States., Johns Hopkins University, Baltimore, MD, United States., University of Virginia, Charlottesville, VA, United States., University of Virginia, Charlottesville, United States., Karmanos Cancer Institute, Detroit, MI, United States., University of Michigan Medical School, Ann Arbor, Michigan, United States., University of Virginia Health System, Charlottesville, VA, United States.