Abstract 4096: Clinical study of personalized neoantigen-based cancer vaccine in the treatment of advanced SCLC patients with brain metastasis: A case report

Abstract

Abstract Background: Tumor neoantigens arising from somatic mutations are less likely to be subjected to central immune tolerance and therefore the attractive targets for designing cancer vaccine. The personalized neoantigen-based cancer vaccine, a passive immunotherapy based on the theory of adaptive immune responses, has been developed rapidly in recent years. Case Presentation: A 75-year-old male small cell of lung carcinoma (SCLC) patient with brain metastasis, who have experienced multiple chemotherapy resistance, and disease relapse after PD-1 therapy, was enrolled in this study. Whole-exome sequencing (WES) and RNA-seq were used to evaluate patient’s mutation burden and to predict the potential neoantigens. Twelve neoantigen peptides were selected and then were synthesized to generate autologous dendritic cell (DC)-based neoantigen vaccine. At last, 1.5 × 108 DC-based neoantigen vaccine was subcutaneously injected into the patient’s body to evaluate the treatment efficacy. By following-up to 10 months after vaccination, we observed an objective response with all brain metastases regressed. The immunogenicity of each of the 12 neo-epitope administered in this study was analyzed by IFNγ ELISpot in CD4+ and CD8+ T cells in pre- and post-vaccination blood samples. Responses were detected against 66.67% (8/12) of the predicted neo-epitope. Conclusions: The autologous DC-based neoantigen cancer vaccine can effectively trigger a positive immune response to patients’ tumor and prolong patients’ survival. The vaccination can also augment the anti-tumor response of T cells by targeting other nonsynonymous mutation-derived neoepitopes. Therefore, these data demonstrated that the autologous DC-based neoantigen cancer vaccine is safe and effective in eliciting a broad antitumor immunity. Moreover, our work has introduced a framework for testing neoantigen-based vaccine combinatorial strategies in patients with advanced recurrent cancers. Citation Format: Song Gao, Yongchao Li, Zhenyu Ding, Heng Xu, Jiaqian Wang, Xianling Guo, Juemin Fang, Guochao Wei, Huanlong Qin, Yuquan Wei, Qing Xu, Li Yang. Clinical study of personalized neoantigen-based cancer vaccine in the treatment of advanced SCLC patients with brain metastasis: A case report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4096.