CELL INTELLIGENCE · 肿瘤细胞治疗研究

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. Cancer cells build up unique changes in their DNA that healthy cells do not have. Some of these changes create new, abnormal proteins on the surface of cancer cells, called neoantigens, which the immune system can learn to recognize as foreign. Because neoantigens exist only on cancer cells, treatments built around them can, in principle, attack tumors while leaving healthy tissue largely untouched. This review brings together current knowledge on where neoantigens come from, how they are found, and how they are being used to treat cancer. Neoantigens can arise from several kinds of DNA and RNA changes and from viruses in some cancers. Modern gene-sequencing technology and computer prediction tools now make it possible to identify a patient’s own neoantigens from a tumor sample, opening the door to personalized cancer vaccines, engineered immune cells, and antibody-based treatments tailored to each patient. Cancers with many DNA mutations, such as melanoma and some lung cancers, tend to respond well to these approaches, while cancers with fewer mutations, such as pancreatic and prostate cancer, are harder to treat this way and often need to be combined with other therapies. Important challenges remain, including the cost and complexity of making a personalized treatment for each patient, the ability of tumors to change and hide from the immune system, and the need for larger clinical trials. Even so, neoantigen-based treatments represent one of the most promising directions in personalized cancer care.