Background: Sip-T, an autologous cellular immunotherapy approved in the US for pts with asymptomatic/minimally symptomatic mCRPC, is produced by culturing peripheral blood mononuclear cells with the immunogen PA2024 (prostatic acid phosphatase [PAP] conjugated to granulocyte macrophage colony-stimulating factor). A biomarker that can identify mCRPC pts who are likely to respond well to sip-T may inform therapeutic decisions. PA2024 and PAP cellular and humoral immune responses induced by sip-T correlate with prolonged OS (Sheikh, CCI 2013;62:137). Robust CTL activity post sip-T treatment has been reported (Drake, ASCO 2017). We investigated the relationship between sip-T lytic activity (using CD107a expression, a cell surface surrogate marker) and OS in mCRPC pts. Methods: PA2024- and PAP-specific CD8+ T (CTL) cells expressing CD107a were identified via flow cytometry at baseline (BL, prior to sip-T infusion), and at 6 and 26 weeks (wks) post-sip-T in pts who were treated in 2 clinical trials (STRIDE: NCT01981122, n = 12 and STAMP: NCT01487863, n = 10), and 3 healthy volunteers (control). Results: CTL activity was significantly (p < 0.0001) increased in response to PA2024 and PAP at wks 6 and 26 post-sip-T vs BL. A strong correlation between PAP and PA2024-specific CTL activity was seen at wk 26 (Pearson’s R = 0.8973, p < 0.0001), but not at BL or wk 6. At wk 26, there were positive correlations between both PAP-specific CTL activity (R = 0.5187, p = 0.0134) and PA2024-specific CTL activity (R = 0.6735, p = 0.0006) and OS. Median OS for pts with PAP- or PA2024-specific CD107a expression above or below the median CTL activity at 26 wks was 37.1 and 25.2 months, respectively. Conclusions: These analyses demonstrate that sip-T induces a robust PAP-specific CTL activity, indicative of tumor lytic activity, which is positively correlated with prolonged OS in mCRPC pts. This finding is a significant addition to the elucidation of the mechanism of sip-T induced immune responses and OS benefit. Clinical trial information: STRIDE: NCT01981122, STAMP: NCT01487863.