Combination of CIK cells with oncolytic viruses: A potential Immunovirotherapy strategy for the treatment of solid tumors

Cytokine-induced killer (CIK) cells represent a promising cellular immunotherapy, characterized by potent cytotoxicity, major histocompatibility complex (MHC)-unrestricted tumor recognition, and ease of ex vivo expansion. Despite these properties, their clinical efficacy against solid tumors remains limited by poor tumor infiltration, limited in vivo persistence, immunosuppressive mechanisms with in the tumor microenvironment (TME), and physical barriers imposed by the dense extracellular matrix (ECM). Oncolytic viruses (OVs) are being investigated as anticancer agents for their tumor-selective replication, induction of immunogenic cell death, and capacity to remodel the TME. OVs can disseminate within solid tumors and penetrate tumor tissue more effectively than cell-based therapies alone. Beyond direct oncolysis, OV-induced tumor cell death promotes systemic antitumor immunity through the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Preclinical studies further suggest that CIK cells can serve as cellular vehicles for OV delivery, protecting viral particles from premature immune clearance and improving intratumoral viral replication and spread. On this basis, combining OVs with CIK cells offers a mechanistically coherent strategy that couples OV-mediated oncolysis and immune activation with the cytotoxic function of effector immune cells. This review explores the molecular rationale for CIK-OV combination immunovirotherapy, summarizes current preclinical and clinical evidence, and discusses the opportunities and limitations of this combinatorial approach for solid tumor treatment.