CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients

Abstract

Objective. To evaluate immune responses and clinical outcomes for combined oregovomab and chemotherapy treatment of patients with recurrent ovarian cancer. Methods. Patients with advanced recurrent ovarian cancer were administered oregovomab over 12 weeks before chemotherapy, then optionally concurrent with chemotherapy × 2. Antibody responses, including human anti-mouse antibody (HAMA), anti-idiotypic antibody (Ab2) and anti-CA125, were assessed by ELISA; T-cell responses to CA125, autologous tumor and oregovomab by interferon (IFN)-γ enzyme-linked immunoSPOT (ELISPOT) were also evaluated. Clinical outcomes were recorded. Results. Twenty patients were enrolled; median follow-up was 15.8 months. Oregovomab was well tolerated and did not produce drug-related serious adverse reactions. In 15/19 (79%) patients, robust treatment-emergent humoral responses were observed to the constant (HAMA) and variable region (Ab2) of oregovomab, and 2/19 (11%) patients developed anti-CA125 antibodies. Significant increases in T-cell responses were measured in 7/18 (39%) patients in response to CA125, in 5/8 (63%) patients in response to autologous tumor and in 9/18 (50%) patients in response to oregovomab. Immune responses appeared by week 12 (four doses) and were generally maintained or augmented in patients continuing combined treatment with oregovomab and chemotherapy. Median survival was 70.4 weeks (4.6–141.6 weeks), and the median progression-free interval was 11 weeks (2.6–114.6 weeks). Patients who mounted a T-cell response to CA125 and/or autologous tumor showed significantly improved survival (median not reached vs. 51.9 weeks, P = 0.002) compared to patients who did not. Conclusions. Oregovomab was well tolerated and induced multiple antigen-specific immune responses, maintained during concomitant chemotherapy. A significant survival benefit was observed in patients mounting a T-cell response to CA125 and/or autologous tumor.