Correlation of interferon-g (IFN-γ) response with survival in a phase II hyperacute (HAL) immunotherapy trial for non-small cell lung cancer (NSCLC).

Abstract

2571 Background: Lung cancer is the leading cause of cancer-related mortality. Patients progressing after initial systemic therapy have a poor prognosis. Thus, new therapies are needed. HAL immunotherapy exploits the hyperacute rejection of a xenotransplant as defense mechanism to initiate anti-tumor immune response by administering genetically modified allogeneic tumor cells expressing the αGal moieties on their cell surface. HAL immunotherapy utilizes αGal epitopes and natural human antibodies (Ab) against these targets as the proposed mechanism for anti-tumor immunity. Methods: We completed a phase II study of HAL immunotherapy in patients with metastatic or recurrent NSCLC, age ≥18, ECOG PS ≤2, ≤2 prior systemic therapies. Trial objectives were to determine response rate, safety and immunological responses. Patients received 300 x 106 HAL cells every 2 weeks for 8 doses. Response was determined using RECIST and adverse events were assessed using CTCAE v3. Immune responses were assessed by changes in serum anti-αGal titers and IFN-γ response. Results: Twenty-eight patients were treated. Eight (29%) demonstrated stable disease (SD) ≥16 wks including one patient that initially progressed and later regressed, surviving over 40 months. Median overall survival (OS) was 11.3 months (95% CI 3.8-21.9). Post vaccination, all patients responded by increasing anti-αGal Ab levels (2-100 fold) and 61% (11/18) of tested patients showed increases in IFN-γ levels (by ELISPOT). Interestingly, patients with increased IFN-γ responses after vaccination (>10-500 fold-increase compared to baseline) had a median survival of 21.9 months compared to 5.5 months in patients with lesser IFN-γ responses after vaccination (p<0.001). In addition, patients with higher IFN-γ responses showed reactivity to a NSCLC cell line that was not a component of HAL, suggesting cross-priming to shared tumor antigens. Conclusions: HAL immunotherapy is safe and feasible. The median survival compared favorably to that reported in patients receiving 2nd line chemotherapy for relapsed or advanced NSCLC. The correlation between IFN-γ response and survival is highly encouraging.