Neoantigen in cancer immunotherapy: mechanism, therapeutic strategies and future perspectives.

Abstract

Neoantigens are tumor-specific antigens resulting from genetic, transcriptomic, and proteomic changes, making them a promising avenue for personalized cancer immunotherapy due to their unique specificity and strong immunogenicity. They arise through various mechanisms like SNVs, INDELs, SVs, alternative splicing, post-translational modifications, and viral oncoproteins. Neoantigen-based therapies, including personalized vaccines, adoptive T-cell therapies, and immune checkpoint inhibitors, have demonstrated considerable potential in both preclinical and clinical settings. Tumors with high mutational burdens, like melanoma and lung cancers, show significant neoantigen-driven immune responses. Progress in cancer treatment is highlighted by the need for combinatorial approaches in tumors with low neoantigen loads, such as pancreatic and prostate cancers, to boost immunogenicity. Advances in computational tools and next-generation sequencing support accurate neoantigen identification for personalized therapies. However, challenges remain, including tumor heterogeneity and immune evasion. Innovative solutions such as machine learning for neoantigen prediction and the use of lipid nanoparticles, alongside radiotherapy and chemotherapy, are being developed to overcome these limitations. Future strategies may involve integrating multi-omics data, next-generation vaccines, and CRISPR-Cas9 gene editing technologies to enhance therapeutic precision. Overall, despite existing challenges, neoantigen-targeted immunotherapies hold promise for advancing precision oncology and improving patient outcomes.