The association of humoral antigen spread (AgS) with cytotoxic T lymphocyte (CTL) activity after sipuleucel-T (sip-T) treatment in two phase II clinical studies: STAMP and STRIDE.

Abstract

112 Background: Sip-T is an FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. Sip-T generates CTL and humoral antigen activity, as measured by CD107a expression on PAP or PA2024 specific CD8+ T cells. These specific CTL activities were correlated with improved overall survival in several studies STAMP (NCT01487863) and STRIDE (NCT01981122) [1]. We examined whether CTL activity enables humoral response generation, hypothesizing that killing a target cell with immunotherapy releases antigens that generate a secondary antibody response, extending the effect. Methods: Using samples from patients who received sip-T in these studies, correlation between CTL activity and AgS responses to primary (PA2024, PAP) and secondary (PSA, LGALS3, LGALS8, KRAS, ERAS, KLK2) antibodies over time was assessed. Using R statistics software, a Wilcoxon signed rank test assessed differences across time (Wk, week: WK0, week 0, etc) and Spearman rank test for correlation between CTL activity and AgS responses. Results: In STAMP, PAP-specific CTL activity at WK0 was positively correlated with LGALS3 antibody responses at WK6, WK10, WK14 and WK26; likewise, PAP-specific CTL activity at WK6 was positively correlated with antibody response to PAP at WK0 (P = 0.035). In STRIDE, PAP-specific CTL activities at WK0 and both PAP- and PA2024-specific CTL activities at WK6 were positively correlated with LGALS8 antibody response at WK52. Plus, PAP- and PA2024- specific CTL activities at WK6 had significant, positive correlation with PA2024 antibody responses at WK0. In both, PA2024-specific CTL activity at WK26 was positively correlated with number of secondary antigen responses at WK10 and WK14. Conclusions: In all, PA2024-specific CTL activity at WK6 was positively correlated with antibody response to primary antigens (PA2024 and PAP) and 4 secondary antigens – PSA, KRAS, ERAS and KLK2 at multiple time points. In summary, treatment with sip-T in mCRPC appears to invoke the tumor immunity cycle, wherein tumor cell death releases compounds that act as secondary epitopes resulting in antigen spread. [1] DOI: 10.1158/1078-0432.CCR-18-0638. Clinical trial information: NCT01487863.