Knight Cancer Institute, Oregon Health & Science University, Portland, OR
Tomasz M. Beer , John Corman , Raymond S. Lance , Dwayne Campogan , Tuyen Vu , Heather Haynes , Nancy N. Chang , Nadeem Anwar Sheikh , Brendan D. Curti
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
Endpoint median (range) | P10-1 (n=7) | mCRPC pts (n=100–118) | ||
---|---|---|---|---|
BL | Wk 6 | BL | Wk 6 | |
ELISPOT count(per 300,000 PBMC) | ||||
PA2024 | 43 (0–362) | 249 (0–718) | 1 (0–66) | 16 (0–503) |
PAP | 48 (0–477) | 65 (4–643) | 0 (0–103) | 1 (0–398) |
Proliferation stimulation index | ||||
PA2024 | 30 (1–52) | 26 (1–118) | 1 (0–24) | 10 (1–90) |
PAP | 6 (1–28) | 7 (1–19) | 1 (0–100) | 1 (0–96) |
IgG + IgM antibody titers x103 | ||||
PA2024 | 26 (0–205) | 410 (1–410)* | 1 (0–410) | 51 (0–410) |
PAP | 6 (0–51) | 51 (1–410)* | 2 (0–410) | 26 (0–410) |
*p<0.05 vs BL
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Abstract Disclosures
2018 ASCO Annual Meeting
First Author: Charles G. Drake
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2024 ASCO Genitourinary Cancers Symposium
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