Boosting long-term immune responses to sipuleucel-T (sip-T) by retreatment of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

196 Background: Sip-T, an autologous cellular immunotherapy for asymptomatic/minimally symptomatic mCRPC, induces immune responses to target antigens prostatic acid phosphatase (PAP) and PA2024, a recombinant protein of PAP and granulocyte macrophage colony-stimulating factor. Immune responses with sip-T correlate with overall survival. PROTECT (phase 3 NCT00779402) assessed sip-T in biochemically recurrent androgen-dependent PC. PROTECT pts developing mCRPC were eligible for P10-1 (phase 2 NCT01338012). Methods: PROTECT pts (sip-T arm) were retreated with sip-T in mCRPC. Antigen presenting cell (APC) activation (CD54 molecule ratio after and before culture with PA2024), cellular (PA2024/PAP ELISPOT; T cell proliferation) and humoral responses were assessed and compared with treatment-naïve mCRPC pts (IMPACT NCT00065442; STAMP NCT01487863; STRIDE NCT01981122). Results: Caucasian men (n=8), median follow-up 9.2 y and age 74 y, had an ECOG PS of 0 (75%) or 1. Median APC activation with sip-T infusion 1 was ~3-fold higher in P10-1 (20; n=7) vs treatment-naïve mCRPC pts (7; n=447). In P10-1, high magnitude cellular and humoral responses were seen at baseline (BL) (Table). Immune memory was heterogeneous, strong BL humoral and/or robust cellular memory was observed. Sip-T boosted PA2024/PAP cellular and humoral responses (Table). Immune responses were maintained up to wk 52, and were higher over time vs 1st time treated mCRPC pts. Conclusions: Sip-T in an earlier disease setting generated sustained antigen-specific immune memory lasting up to 10 y. Consistent with vaccine-induced immune responses, sip-T retreatment rapidly boosted both cellular and humoral antigen-specific responses in mCRPC pts. Clinical trial information: NCT01338012. [Table: see text]