Abstract 5507: Immunological findings in a phase II immunotherapy study using allogeneic lung cancer cells modified to express alpha(1,3)galactosyltransferase in advanced non-small cell lung cancer (NSCLC)

Abstract

Abstract Background: Alpha(1,3)galactose carbohydrate (αGal) epitopes are highly immunogenic in man. In animal models, vaccination with αGal expressing tumor cells induced rejection of tumor and improved survival. In a phase II anti-tumor immunotherapy study, we evaluated the safety, anticancer activity and immunogenicity of allogeneic human lung cancer cells expressing αGal epitopes HyperAcute-Lung (HAL) vaccines. Methods: Patients with advanced NSCLC received intradermal injections of 300 million HAL vaccine cells every 2 weeks for up to eight doses. Anti-αGal (IgG) and anti-CEA antibodies (Ab) were monitored by ELISA. Cellular immune responses were evaluated by ELISPOT assay (IFN-γ and IL-5). Serum was collected before and at several time points post-immunization. PBMC were collected prior to immunization, after the 4th vaccination and after 8 vaccinations. PBMC were cultured with autologous dendritic cells (DC) pulsed with one of 4 irradiated NSCLC cell lines, three of which were the parental (wild type) cell lines used to generate the vaccine. The fourth was a NSCLC line that was not a component of the vaccine. We compared the reactivity of PBMC stimulated with DC pulsed with these tumor cells pre- and post-immunization in 18 patients with available samples. Results: All patients demonstrated anti-αGal Ab prior to immunization and all responded to vaccination by increasing anti-αGal Ab 2 to 100-fold. Thirty-two patients were tested for anti-CEA Ab. Twenty patients showed significant increases in anti-CEA Ab after immunization. IFN-γ release was detected in 10 of 18 patients evaluated. Patients demonstrating IFN-γ release by ELISPOT after immunization had a median overall survival of 92 weeks (range 40 to 157) comparing favorably with 33.5 weeks (range, 12 to 200) in patients that showed little IFN-γ response. The majority of patients tested showed IL-5 induction after vaccination. In both assays, the HAL1 and HAL2 vaccine cell lines induced greater reactivity on ELISPOT. Patients responding with higher levels of IFN-γ and IL-5 also showed reactivity to the NSCLC cell line that was not a component of the vaccine suggesting that reactivity and possibly cross-priming to shared tumor antigens is induced after vaccination with HyperAcute immunotherapy. Conclusion: Hyperacute anti-tumor immunotherapy induced humoral and cellular responses. Cytokine expression, especially IFN-γ, might be predictive for increased survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5507. doi:10.1158/1538-7445.AM2011-5507