Gene Editing in Cancer Immunotherapy: Mechanisms, Advancements, Limitations and Future Directions

Gene editing has emerged as a transformative approach in cancer immunotherapy. Several gene editing tools have been employed for precise modification of the DNA of immune cells, enhancing their ability to target and eliminate cancer cells. This review examines the evolution and applications of key gene-editing tools, such as CRISPR-Cas9, TALENs, ZFNs, and recent innovations like base and prime editing in the field of cancer immunotherapy. Promising results have been observed in therapies such as CAR-T and tumor-infiltrating lymphocyte (TIL) treatments, which have shown success in cancers like leukemia and lymphoma. These technologies improve immune system function by disrupting checkpoints, boosting cytokine production, and modifying tumor microenvironments. Significant clinical trials have demonstrated promising outcomes, such as CRISPR-Cas9-engineered T cells targeting refractory cancers, which showed improved efficacy and safety. However, despite these advancements, there have been limitations, including off-target effects, delivery inefficiencies, immunogenicity, and ethical concerns, alongside the high costs that hinder widespread adoption. Future directions for gene editing in cancer therapy include the integration of AI and machine learning to enhance target accuracy and guide RNA design, as well as novel gene-editing systems such as the I-C Cascade-Cas3, which facilitates large-scale genomic deletions. Furthermore, CRISPR-based epigenome editing holds promise for further advancing cancer therapies. These innovations, combined with optimized delivery methods, are expected to improve the precision, efficacy, and accessibility of gene editing in cancer immunotherapy.