Immune evaluation study of sipuleucel-T (Sip-T) in African-American and European-American men with castration-resistant prostate cancer.

Abstract

206 Background: Sipuleucel-T (Sip-T) is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients and targets the prostate antigen, prostatic acid phosphatase (PAP). In Phase 3 trials of Sip-T, there was a suggestion that AA men treated with Sip-T had enhanced OS benefit compared to the general population. This study was designed to evaluate the peripheral immune parameters in African American (AA) and European American (EA) prostate cancer patients receiving Sip-T treatment. Methods: Peripheral blood mononuclear cell and serum samples were evaluated for T- and B cell responses in 10 AA and 20 EA men with mCRPC. Antigen-specific T cell response was measured by IFN-γ Elispots, antigen-specific IgG and IgM responses to PA2024, PAP, PSMA, and PSA by ELISA, cytokine and chemokine levels by luminex and immune cell phenotyping by flow cytometry in the PBMC at baseline, 6-, and 10-week time points after completion of Sip-T treatment. Results: IFN-γ EliSpots were ≥ 2-fold higher when stimulated with PA2024 and PAP antigens in AA compared to EA patients post treatment. Humoral immune responses (IgM) to PA2024 and PAP was ≥ 100-fold higher at 6 and 10 weeks after completion of the 3rd infusion in both groups, however, there were no appreciable differences in antibody levels between AA and EA patients. Interestingly, there were ≥ 2-fold higher IgM titers for non-targeted PSA and PSMA at 6 and 10 weeks post treatment compared to baseline levels in both groups suggesting epitope spreading. Humoral responses (IgM) to PAP, PSA and PSMA at baseline were higher in AA patients compared to EA patients. The Th1 and Th2 cytokine and chemokine profiles showed no difference between AA and EA men except for inflammatory chemokine IL-8 which gradually decreased at 6 and 10 weeks from the baseline in AA patients compared to the transient decreases in EA patients. Conclusions: Our preliminary results are suggestive of slightly increased IFN-γ EliSpot responses in AA patients compared to EA patients. Both, AA and EA showed potent IgM antibody response to PA2024 and PAP antigens post treatment compared to the baseline levels. Clinical trial information: NCT01727154.