Abstract LB-076: Personal neoantigen immunotherapy in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers and the leading causes of mortality in China with limited therapeutic options. To investigate whether neoantigens could induce tumor specific immune responses in patients with HCC, neoantigen stimulating cellular therapy (neo-MASCT) was applied after radical resection. Neo-MASCT was a cell-based immunotherapy with injections of mature dendritic cells (DCs) loaded with a peptide pool of multiple shared tumor associated antigens (TAAs) and several personalized neoantigens followed by autologous T cells stimulated by these DCs. To obtain neoantigens, fresh tumor samples were acquired immediately after biopsy or surgery for subsequently WES and RNAseq. All mutations including SNV, non-frame shift insert/deletion (Indel), and neoORF were detected by comparing NGS data from tumors to normal tissues. All neo-epitope candidates were predicted by our own proprietary algorithm MASNEO according to the patient’s HLA class I genotypes. Long neoantigen peptides containing 25-31 amino acids with higher affinities were selected for further synthesis and treatment. Peptides containing multiple neo-epitopes were preferred. Until now, eight patients had received neo-MASCT, and seven of them were tested for specific immune responses against both TAAs and neoantigens using IFNγ Elispot assay. The results showed that Neo-MASCT induced TAA-specific immune responses in five patients (5/7, 71%), and induced neoantigen-specific immune responses in six patients (6/7, 86%), respectively. One patient demonstrated specific T cell responses against all the five neoantigen peptides (5/5, 100%) after neo-MASCT treatment. The average responsive rate of neoantigens was 65% (22/34 peptides) in the six responding patients. In conclusion, our results demonstrate that neo-MASCT is well-tolerated in HCC patients and elicits immune responses against multiple tumor antigens, especially personalized neoantigens. We will continuously monitor the immune responses against neoantigens, and use the results to train and optimize our predicting algorithm. We will also evaluate the clinical benefit of neo-MASCT in further clinical trials with more patients. Citation Format: Sui Peng, Zhenwei Peng, Lixia Xu, Jie Mei, Longqing Tang, Yanyan Han, Ming Kuang. Personal neoantigen immunotherapy in hepatocellular carcinoma [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 LB-076.