新抗原疫苗增强抗 PD-1 对小鼠肝细胞癌的抗肿瘤效果

Immune checkpoint inhibitors are groundbreaking resources for cancer therapy.

However, only a few patients with hepatocellular carcinoma (HCC) have shown positive responses to anti-PD-1 therapy. Neoantigens are sequence-altered proteins resulting from somatic mutations in cancer.

This study identified the neoantigens of Hep-55. 1C and Dt81 Hepa1-6 HCCs by comparing their whole exome sequences with those of a normal C57BL/6 mouse liver. Immunogenic long peptides were pooled as peptide vaccines. The vaccination elicited tumor-reactive immune responses in C57BL/6 mice, as demonstrated by IFN-γ ELISPOT and an in vitro killing assay of splenocytes.

In the treatment of three mouse HCC models, combined neoantigen vaccination and anti-PD-1 resulted in more significant tumor regression than monotherapies. Flow cytometry of the tumor-infiltrating lymphocytes showed decreased Treg cells and monocytic myeloid-derived suppressor cells, increased CD8 + T cells, enhanced granzyme B expression, and reduced exhaustion-related markers PD-1 and Lag-3 on CD8 + T cells in the combination group.

These findings provide a strong rationale for conducting clinical studies of using neoantigen vaccination in combination with anti-PD-1 to treat patients with HCC.