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Research Article Volume 17 Issue 2
Clinical outcomes of CAR-NK cell therapy: a systematic review of early-phase trials
Manal M E Ahmed, Asmaa Noureen, Ayesha Rafiq
Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore (UOL), Pakistan
Received: March 15, 2026 | Published: March 27, 2026
Citation: Ahmed MME, Noureen A, Rafiq A. Clinical outcomes of CAR-NK cell therapy: a systematic review of early-phase trials. J Cancer Prev Curr Res. 2026;17(2):32‒39. DOI: 10.15406/jcpcr.2026.17.00603
Abstract
Background: Chimeric antigen receptor–engineered natural killer (CAR-NK) cells represent an emerging platform in cellular immunotherapy that combines antigen-specific targeting with the intrinsic cytotoxicity of natural killer cells. Compared with CAR-T therapy, CAR-NK cells offer several theoretical advantages, including a lower incidence of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), minimal risk of graft-versus-host disease (GVHD), and the potential for standardized allogeneic “off-the-shelf” products. However, clinical evidence remains fragmented across early-phase trials. Objective: To systematically evaluate the clinical efficacy, survival outcomes, persistence, and safety profile of CAR-NK cell therapies across hematologic and solid malignancies. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, Web of Science, Scopus, and ClinicalTrials.gov were searched from January 2000 to December 2024 for clinical studies evaluating CAR- NK therapy in cancer patients. Primary endpoints included overall response rate (ORR) and complete remission (CR). Secondary outcomes included progression-free survival (PFS), overall survival (OS), CAR-NK persistence, and treatment-related adverse events. Pooled estimates were calculated using random-effects models (DerSimonian–Laird). Heterogeneity was assessed using the I² statistic, and publication bias was evaluated by funnel plots and Egger’s regression test. Results: Seventeen clinical studies involving 738 patients were included. The pooled overall response rate (ORR) was 53% (95% CI: 41–65%), while complete remission (CR) occurred in 29% (95% CI: 21–38%). Subgroup analysis revealed significantly higher efficacy in hematologic malignancies (ORR 71%) compared with solid tumors (24%, p < 0.001). Cord blood–derived CAR-NK cells demonstrated the highest response rates (62%) and longest persistence (up to 12 months). The therapy exhibited an excellent safety profile: any-grade CRS occurred in 8.7% of patients, while grade ≥3 CRS occurred in only 1.4%, markedly lower than reported with CAR-T therapies. No cases of GVHD were reported. Conclusion: CAR-NK therapy demonstrates promising antitumor activity with a superior safety profile, particularly in hematologic malignancies. However, efficacy in solid tumors remains limited due to tumor microenvironment barriers and trafficking constraints. Future phase II/III trials, standardized manufacturing strategies, and next-generation engineered CAR-NK platforms are required to fully realize the clinical potential of this therapeutic modality.
Keywords: CAR-NK cells; NK cell therapy; cellular immunotherapy; hematologic malignancies; solid tumors; adoptive cell therapy; systematic review
©2026 Ahmed, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.