Personalized neoantigen vaccine combined with PD-1 blockade increases CD8+tissue-resident memory T-cell infiltration in preclinical hepatocellular carcinoma models

• DOI: 10.1136/jitc-2021-004389
• Publication Date: 2022-09-16T17:07:19Z
• Authors: Hengkai Chen; Zhenli Li; Liman Qiu; Xiuqing Dong; Geng Chen; Yingjun Shi; Linsheng Cai; Wenhan Liu; Honghao Ye; Yang Zhou; Jiahe Ouyang; Zhixiong Cai; Xiaolong Liu
• Keywords: Clinical/Translational Cancer Immunotherapy; 0301 basic medicine; Carcinoma, Hepatocellular; Liver Neoplasms; Programmed Cell Death 1 Receptor; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; CD8-Positive T-Lymphocytes; Cancer Vaccines; 3. Good health; Memory T Cells; Mice; 03 medical and health sciences; Vaccines, Subunit; Tumor Microenvironment; Animals; Peptides; RC254-282

Personalized neoantigen vaccine could induce a robust antitumor immune response in multiple cancers, whose efficacy be further enhanced by combining with programmed cell death 1 blockade (α-PD-1). However, the corresponding and synergistic mechanisms remain largely unclear. Here, we aimed to develop clinically available combinational therapeutic strategy explore its potential hepatocellular carcinoma (HCC).Neoantigen peptide (NeoVAC) for murine HCC line Hepa1-6 was developed optimized screening adjuvant optimization. Then related molecular of NeoVAC combined α-PD-1 were evaluated orthotopic mouse model, single-cell RNA sequencing, tetramer flow cytometry, immunofluorescence, etc. The tumor-killing capacity CD8+ tissue-resident memory T cells (CD8+ TRMs) assessed autologous patient-derived cells.NeoVAC, which consisted seven high immunogenic peptides clinical-grade Poly(I:C), generate strong models. Significantly, improved α-PD-1, 80% durable tumor regression long-term Moreover, in-depth analysis microenvironment showed that percentage TRMs remarkedly increased plus treatment group, positively associated efficacy. In vitro vivo T-cell cytotoxicity assay confirmed sorting from or patient's tissue.This study tumor-specific increasing infiltration, might serve as immune-therapeutic target HCC.