Abstract 5577: Effective personalized neoantigen-based cancer vaccine combined with immune checkpoint inhibitor in the treatment of a patients with advanced squamous cell lung cancer failed with multi-line treatments
Authors: Gao Song , Zhu Zhongzheng , Wang Jiaqian , Fang Juemin , Zhao Yu , Liu Zhuqing , Wei Guochao , Qin Huanlong , Wei Yuquan , Xu Heng , Yang Li , Xu Qing 
Published: September 2020

BACKGROUND: The treatment of squamous cell carcinoma of the lung (SqCC) patients who failed with multi-line treatment is still limited. Immunotherapy with immune checkpoint inhibitors as the main treatment has made a breakthrough in advanced lung cancer. The personalized neoantigen-based cancer vaccine, another immunotherapy based on the theory of adaptive immune responses, has been developed rapidly in recent years. The combination of neoantigen vaccines against anti-PD-1/PD-L1 at the same time (or successively) has obvious appeal as previous clinical trials reported in melanoma, and is likely to be the first combination therapy to be formally examined in clinical trials. Here, We report a case of SqCC treated with dendritic cell-based neoantigen vaccine combined with immune checkpoint inhibitor.

CASE SUMMARY: A 68-year-old male squamous cell carcinoma of the lung patient, who disease relapse after multi-line treatments that including chemotherapy, radiotherapy, targeted therapy, and antiangiogenic therapy, was enrolled in this study. Whole-exome and transcriptome sequencing were used to evaluate patient's mutations and predict the potential neoantigens for vaccine. Seventeen neoantigen peptides were selected and then synthesized to generate autologous dendritic cell (DC)-based neoantigen vaccine. At last, 1.38 × 108 DC-based neoantigen vaccine was subcutaneously injected into the patient's body (on days 1, 7, 15, 22 and 30) in combination with immune checkpoint inhibitor (PD-l antibody, dose 4mg/kg followed by 2 mg/kg biweekly). By following-up to 10 months after vaccination, we found this refractory advanced SqCC patient has achieved partial remission. The immunogenicity of each of the 17 neo-epitopes administered in this study was analyzed by IFNγ ELISpot in CD4+ and CD8+ T cells in blood samples. Responses were detected against 64.71% (11/17) of the predicted neo-epitopes.

CONCLUSION: In summary, these results show that the dendritic cell based neoantigen vaccine combined with immune checkpoint inhibitor is safe and well tolerated in advanced lung cancer patients who failed with multi-line treatments. The neo-antigen vaccine can cause T cell immune response in vivo. The bioinformatics prediction algorithm helps to select high-quality neoantigens. Moreover, our work has introduced a framework for testing neoantigen-based vaccine combinatorial strategies in patients with advanced lung cancer.

Citation Format: Song Gao, Zhongzheng Zhu, Jiaqian Wang, Juemin Fang, Yu Zhao, Zhuqing Liu, Guochao Wei, Huanlong Qin, Yuquan Wei, Heng Xu, Li Yang, Qing Xu. Effective personalized neoantigen-based cancer vaccine combined with immune checkpoint inhibitor in the treatment of a patients with advanced squamous cell lung cancer failed with multi-line treatments [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5577.