NK and CIK Cells in Hematologic Malignancies: Comparative Mechanisms, Clinical Evidence, and Translational...

Hematologic malignancies remain a major cause of morbidity and mortality despite advances in chemotherapy, targeted therapies, and hematopoietic stem cell transplantation. Adaptative cell therapy has emerged as a promising approach, in which natural killer (NK) and cytokine-induced killer (CIK) cells appear as potentially complementary effective platforms.

This review critically compares NK and CIK cells as two adaptive cellular immunotherapy platforms for hematologic malignancies, focusing on their biological properties, antitumor mechanisms, production strategies, clinical evidence, safety profiles, and translational limitations.

NK and CIK cells were comparatively evaluated with respect to their biological properties, antitumor mechanisms, production strategies, clinical evidence, safety profiles, and translational limitations.

NK cells, through the release of perforin-granzyme, death receptor pathways, and antibody-dependent cytotoxicity, perform rapid tumor clearance, allowing for immediate tumor volume reduction, but with limited persistence in vivo. In contrast, in vitro-expanded CIK cells (CD3+CD56+) show robust proliferation and sustained cytotoxicity, with an overall low, but not entirely zero, risk of graft-versus-host disease, supporting long-term immune surveillance. CAR engineering, cytokine-induced memory-like NK cells, and DC-CIK platforms may improve persistence, specificity, and metabolic fitness. Combination strategies with checkpoint inhibitors and standard therapies may enhance antitumor efficacy. However, most evidence is still preliminary and comes mainly from early-phase, single-arm, and heterogeneous studies.

NK and CIK cells may offer complementary benefits rather than direct competitive approaches. Their distinct functional properties provide the biological rationale for future combination or sequential strategies. However, prospective clinical studies are needed to define their efficacy, safety, durability, and optimal clinical application in hematological malignancies.