Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as one effective treatment against complex diseases, including malignancies, infectious disorders, and autoimmune conditions. However, its clinical applications remain hindered by severe side effects, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Recent innovations in genome editing and computational biology, specifically CRISPR/Cas9 and artificial intelligence (AI), offer promising avenues to improve CAR-T safety and efficacy. In this article, we reviewed recent advances in CAR-T therapy, highlighting the key role CRISPR/Cas9 plays in various aspects of CAR-T therapy through gene editing. We then studied and analyzed how AI leverages large datasets and its powerful learning capabilities to advance CAR-T therapies and CRISPR/Cas9. Finally, focusing on CAR-T therapy, we discussed how CRISPR/Cas9 and AI work synergistically to advance the development of CAR-T therapy, including reducing toxic side effects, improving therapeutic efficacy, sustaining long-term outcomes, discovering new therapeutic targets, and ensuring safety monitoring. By combining the predictive power of AI with the precision of CRISPR/Cas9, researchers can develop next-generation immunotherapies that are safe, effective, and tailored to the patients' requirements. This synergy can address previously untreatable diseases and reshape the landscape of precision medicine.
Citation: Jiesheng Cui, Dini Zhang, Guanyu Wang. Combinatorial application of artificial intelligence and CRISPR/Cas9 on the next-generation CAR-T immunotherapy[J]. AIMS Molecular Science, 2025, 12(3): 292-317. doi: 10.3934/molsci.2025018
Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as one effective treatment against complex diseases, including malignancies, infectious disorders, and autoimmune conditions. However, its clinical applications remain hindered by severe side effects, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Recent innovations in genome editing and computational biology, specifically CRISPR/Cas9 and artificial intelligence (AI), offer promising avenues to improve CAR-T safety and efficacy. In this article, we reviewed recent advances in CAR-T therapy, highlighting the key role CRISPR/Cas9 plays in various aspects of CAR-T therapy through gene editing. We then studied and analyzed how AI leverages large datasets and its powerful learning capabilities to advance CAR-T therapies and CRISPR/Cas9. Finally, focusing on CAR-T therapy, we discussed how CRISPR/Cas9 and AI work synergistically to advance the development of CAR-T therapy, including reducing toxic side effects, improving therapeutic efficacy, sustaining long-term outcomes, discovering new therapeutic targets, and ensuring safety monitoring. By combining the predictive power of AI with the precision of CRISPR/Cas9, researchers can develop next-generation immunotherapies that are safe, effective, and tailored to the patients' requirements. This synergy can address previously untreatable diseases and reshape the landscape of precision medicine.
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Figures(4) / Tables(3)
Jiesheng Cui, Dini Zhang, Guanyu Wang. Combinatorial application of artificial intelligence and CRISPR/Cas9 on the next-generation CAR-T immunotherapy[J]. AIMS Molecular Science, 2025, 12(3): 292-317. doi: 10.3934/molsci.2025018
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