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Advances in CAR-T Cell Therapy, Clinical Breakthroughs, Challenges, and Future Directions: A Narrative Review | ||
| Kirkuk Journal of Medical Sciences | ||
| Volume 13, Issue 2, July 2025, Pages 87-94 PDF (589.11 K) | ||
| Document Type: Review article | ||
| DOI: 10.32894/kjms.2025.162601.1167 | ||
| Authors | ||
| Zainab Khalid Khaleel1; Zinah Makki Al-Yozbakee* 2; Farqad M. Alhamdani1; Ban M. Saeed1 | ||
| 1Department of Microbiology, Al-Zahraa College of Medicine, University of Basrah, Basrah, Iraq | ||
| 2Department of Microbiology, College of Medicine, University of Mosul, Mosul, Iraq | ||
| Abstract | ||
| Chimeric antigen receptor T-cell (CAR-T) therapy is a landmark of oncologic immunotherapy, transforming care in selected hematologic malignancies and expanding toward solid tumors and autoimmune diseases. Durable remissions in leukemia and lymphoma are well established, whereas signals in solid tumors remain limited to early-phase studies and a few randomized evaluations. Key challenges persist, including therapy-related toxicities (notably cytokine release syndrome [CRS] and immune effector cell–associated neurotoxicity syndrome [ICANS]), antigen escape and other mechanisms of resistance within the immunosuppressive tumor microenvironment, and substantial logistical and cost barriers. This narrative review synthesizes clinical evidence from phase I–III trials and large real-world cohorts and summarizes advances in manufacturing, delivery, and toxicity mitigation. Literature was identified through PubMed, Embase, Scopus, Web of Science, and major publisher platforms (January 1, 2010–May 31, 2025) using terms such as “chimeric antigen receptor,” “CAR-T,” “bispecific CAR-T,” “dual-targeting CAR-T,” and “solid tumor CAR-T”; high-quality systematic reviews and meta-analyses informed context. Emerging innovations include in vivo approaches using lipid-nanoparticle–encapsulated mRNA to program T cells within the patient, allogeneic “universal” CAR-T candidates edited by CRISPR/Cas9 (e.g., TRAC and B2M) to reduce alloreactivity and enable off-the-shelf use, and computational/AI-aided receptor design to optimize efficacy and predict toxicity. Overall, CAR-T therapy continues to evolve with promising strategies to enhance outcomes and accessibility; however, broader confirmation in well-powered trials, biomarker-guided selection, scalable manufacturing, and equitable cost models remain essential for a widespread impact in refractory diseases. | ||
| Keywords | ||
| CAR-T cell therapy; Hematologic malignancies; Toxicities; Cytokine release syndrome; Gene editing | ||
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