Introduction. Sipuleucel-T is a patient-specific autologous cell product consisting of antigen presenting cells (APCs) loaded with a recombinant fusion protein (PA2024) comprising prostatic acid phosphatase (PAP) linked to GM-CSF. Reported here are immune response data from a randomized Phase 3 trial, D9902B (IMPACT). Methods. 512 subjects with metastatic castrate resistant prostate cancer were randomized (2:1) to receive sipuleucel-T or placebo intravenously every 2 Wks x 3. Serum and peripheral blood mononuclear cells (PBMCs) were obtained at Baseline and at Wks 6, 14, and 26 and cryopreserved; all samples from a single subject were evaluated in the same assay. Humoral responses in cryopreserved subject serum were assessed by ELISA. Cellular responses were assessed by IFNγ ELISPOT and 3H-thymidine T cell proliferation assays. Results. The median CD54 upregulation ratio increased after culture at all 3 treatment weeks in the sipuleucel-T, but not the placebo, arm. The magnitude of APC activation was significantly greater at Wk 2 (10.8-fold) and Wk 4 (11.0-fold) compared to Wk 0 (both P < 0.001). The proportion of subjects with a positive antibody response to PA2024 (antibody titer > 400) increased after treatment with sipuleucel T, rising from 2.0% at baseline to 73.9% at Wk 14. Titers for anti-PA2024 and anti-PAP increased significantly from Wk 0 to Wk 6 after treatment with sipuleucel-T (both P < 0.001), but not placebo. Anti-PA2024 titers increased approx. 60-fold from Baseline at Wks 6 and 14, and anti-PAP titers increased from 10- to 6-fold up to Wk 26. Further analysis of the PA2024-specific humoral isotype revealed class switching from an IgM to IgG response. The proportion of subjects with PA2024-specific IFNγ ELISPOT responses (> 10 spots) increased after treatment with sipuleucel-T. The maximal value observed was 50.8% of subjects at Wk 6 compared with 5.7% at baseline, and specific responses were present at Wk 26. There was little increase in the proportion of subjects with PAP-specific IFNγ ELISPOT responses from Wk 0 to Wk 6. 78.6% of sipuleucel-T subjects mounted anti-PA2024 proliferative responses (stimulation index [SI] > 5). T cell proliferative responses increased significantly from Wk 0 to Wk 6 (P < 0.001) and remained above Wk 0 levels at Wk 26 (SI = 61.5). The PAP-specific proliferative response rose from Wk 0 to Wk 6 (P = 0.071), and remained above Wk 0 levels at Wk 26 (SI = 30.5). Conclusion. Immunogen and PAP-specific responses were observed after treatment with sipuleucel-T but not placebo. The majority of subjects treated with sipuleucel-T had persistent cellular and humoral responses (26 Wks). In addition the humoral class switching data suggest the establishment of a memory response.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2932.

©2010 American Association for Cancer Research
2010