• Cancer immunotherapy with CAR-T and CAR-NK cells
  • Mahdi Mondali,1,*
    1. Imam Hossein Comprehensive University Student


  • Introduction: Immunotherapy based on engineered cells, particularly CAR-T and CAR-NK cells, has brought about a fundamental transformation in cancer treatment over the past decade. CAR-T cells were first successfully used in the treatment of hematologic malignancies such as childhood acute lymphoblastic leukemia and non-Hodgkin lymphomas, resulting in remarkably high clinical response rates {1}. The development of various generations of CARs through the addition of co-stimulatory domains such as CD28 and 4-1BB has led to enhanced stability and antitumor potency of these cells {2}.
  • Methods: This scientific research article, using an analytical-research method and based on a systematic review of credible scientific sources, analyzes the design principles and mechanisms of action of CAR-T and CAR-NK cells, clinical results, limitations, as well as ethical and regulatory considerations. It also examines recent advancements such as multi-specific CARs, TRUCKs, genome editing, and their potential applications in solid tumors. Finally, the future outlook of this field is outlined to define potential research and therapeutic pathways.
  • Results: Study results indicate that CAR-T therapy is considered a standard treatment for certain blood cancers and has achieved high response rates and long-term survival in patients; however, side effects such as cytokine release syndrome and neurotoxicity have posed significant limitations {3}. In contrast, CAR-NK cells have been introduced in early clinical trials with notable efficacy, lower toxicity, and the potential for allogeneic (off-the-shelf) production, although their persistence and proliferation remain inferior to CAR-T cells and represent a major challenge. Preclinical evidence also suggests that combining these approaches with technologies such as gene editing and optimized costimulatory molecules could help overcome these limitations.
  • Conclusion: Immunotherapy using CAR-T and CAR-NK cells holds revolutionary potential in cancer treatment. CAR-T is currently established as an effective therapy for hematologic malignancies, yet its application is limited by side effects and high costs. CAR-NK offers a promising future outlook due to its improved safety profile and allogeneic applicability, although it requires more extensive clinical trials. Recent advancements in CAR design and integration with genetic technologies could open new horizons for treating solid tumors and reducing adverse effects.
  • Keywords: CAR-T, CAR-NK, Cancer Immunotherapy, Hematologic Malignancies, Solid Tumors