Cytokine-Induced Killer Cells As Pharmacological Tools for Cancer Immunotherapy

Abstract

Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3+CD56+ natural killer T cells, which can be easily expanded in vitro from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor. Furthermore, we briefly sum up the clinical trials on CIK cells and compare the effect of clinical CIK therapy with other immunotherapies. Finally, further research is needed to clarify the pharmacological mechanism of CIK and provide evidence to formulate uniform culturing criteria for CIK expansion.

Maintenance therapy with ex vivo expanded lymphokine‐activated killer cells and rituximab in patients with follicular lymphoma is safe and may delay disease progression

“…Most CD8 + cells exhibited high CD56 expression, showing a phenotype corresponding to cytokine‐induced killer cells (CIK). This lineage exhibits high cytotoxic activity by mediating cell lysis independently of major histocompatibility complex and releasing cytokines (Pittari et al , 2015; Gao et al , 2017). Thus, rhIL‐2 expanded host cells could mediate antitumour actions through NK‐dependent ADCC, and LAK and CIK activities.…”

Cellular therapy: Adoptive immunotherapy with expanded natural killer cells

“…The resulting product exhibits innate anti‐tumor cytotoxicity in a non‐MHC restricted manner, primarily using NKG2D as the activating receptor. Allogeneic donor CIK have been studied as adoptive cell therapy for both solid and hematologic malignancies, and have a high safety profile with a low incidence of GvHD …”

“…The resulting product exhibits innate anti-tumor cytotoxicity in a non-MHC restricted manner, primarily using NKG2D as the activating receptor. Allogeneic donor CIK have been studied as adoptive cell therapy for both solid and hematologic malignancies, 12 and have a high safety profile with a low incidence of GvHD. 13,14 The ability to harvest large numbers of peripheral blood lymphocytes through leukapheresis, deplete alloreactive T cells, and activate the remaining NK cells with IL-2 has enabled NK cell adoptive immunotherapy, but this process is expensive, invasive, and remains limited to infusion of a single cell dose of typically less than 2 × 10 7 NK cells/kg.…”

The priming role of dendritic cells on the cancer cytotoxic effects of cytokine-induced killer cells

“…The immediate benefit is to limit or prevent unwanted side effects. In the types of immune cells studied, two candidates emerged from both arms of the immune system: dendritic cells (DCs) from innate immunity 27 and cytokine-induced killer cells (CIK cells) from adaptive immunity 28 . Dendritic cells (DCs) are the most professional antigen-presenting cells (APC) 29 .…”