Engineering In Vitro Organ‐Structured Tumor Model for Evaluating Neoantigen‐Specific T Cell Responses in Hepatocellular Carcinoma

Abstract Neoantigens derived from somatic mutations in cancer cells can induce antigen‐specific T‐cell immune response for immunotherapy. However, the 3D models assessing neoepitope immunogenicity and efficacy of anti‐tumor to neoantigens are less than perfect. Here, a tumor model based on recellularized liver matrix is leveraged with HepG2 investigate T cell cytotoxic reactivity toward hepatocellular carcinoma (HCC) neoantigens. The whole exome sequencing (WES) data 364 HCC patients Cancer Genome Atlas database collected 25 highly potential immunogenic human leukocyte antigen (HLA)‐A*02:01 molecule silico predicted. Six neoantigen candidates functionally validated high by measuring cellular interferon‐ γ secretion cytotoxicity during neoantigen‐specific responses vitro. Then, minigene six identified peptides constructed minigene‐modified GFP‐HepG2 generated. Neoantigen‐specific observed secreted Granzyme B, IFN‐ , PD‐1 when targeting RLM model. Overall, provides novel strategy preclinical assessment response, which helps develop personalized vaccines immunotherapy treatments patients.