Cancer Immunotherapy with Cytokine-Induced Killer Cells

Abstract

Cytokine-induced killer (CIK) cells form under certain stimulation conditions in cultures of peripheral blood mononuclear cells (PBMCs). They are a heterogeneous immune cell population and contain a high percentage of cells with a mixed T-NK phenotype (CD3+CD56+). The ready availability of a lymphocyte source, together with the high proliferative rate and potent anti-tumor activity of CIK cells, has allowed their use as immunotherapy in a wide variety of neoplasms. Cytotoxicity mediated by CD3+CD56+ T cells depends on the major histocompatibility antigen (MHC)-independent recognition of tumor cells and the activation of signaling pathways through the natural killer group 2 member D (NKG2D) cell-surface receptor. Clinical trials have demonstrated the feasibility and efficacy of CIK cell immunotherapy even in advanced stage cancer patients or those that have not responded to first-line treatment. This review summarizes biological and technical aspects of CIK cells, as well as past and current clinical trials and future trends in this form of immunotherapy.

Cytokine-Induced Killer Cells as an Adoptive Cellular Immunotherapy Strategy for Hepatocellular Carcinoma

“…The results of CD3 and CD56 phenotypes showed a very significant increase in expression versus culture duration. This finding was supported by Mata-Molanes et al [17], who reported that after 14 days of culture, the percentage of CD3 + CD56 + subset reaches 20 to 30% of the total CIK cells. Guo et al [30], who cultured CIK cells from healthy volunteers' blood donors for 14 days, reported CD3 + CD56 + proportion on day 14 as 25.31 ± 7.42%.…”

“…CIK cells, as the most frequently used ACT, are a heterogeneous cell population including natural killer T (NKT) cells (CD3 + CD56 + ), T cells (CD3 + CD56 − ), and NK cells (CD3 − CD56 + ) cells. Normally, the most cytotoxic cells with double T/NK phenotype are uncommon but present (1% to 5%) in circulating blood [16]; yet, after in vitro expansion for 14 days, they may reach 20 to 30% of the total CIK cells [17]. Most of these NKT cells have been shown to be derived from the T cells and not from NK cells [18].…”

Efficacy of adjuvant cytokine-induced killer cell immunotherapy in patients with colorectal cancer after radical resection

“…Several clinical studies have confirmed survival benefit and safety of CIK cell immunotherapy for patients with cancers. 14,25 Recently, the role of CIK cell treatment in patients with CRC was also reported. 22,[26][27][28] However, to date, there is only one study on the therapeutic effects of adjuvant CIK cell treatment in patients with CRC after surgery, and their results were limited by small sample size and short follow-up time.…”

Retrospective analysis of the efficacy of cytokine‐induced killer cell immunotherapy combined with first‐line chemotherapy in patients with metastatic colorectal cancer

“…4,7 A series of studies have demonstrated the efficacy of adoptive cell immunotherapy, including tumorinfiltrating lymphocytes, antigen-specific T lymphocytes, cytokine-induced killer (CIK) cells and chimeric antigen receptor (CAR) T cells. [8][9][10][11] Among them, CIK cells have characteristics of rapid proliferation, strong antitumor activity, broad spectrum of antitumor activity and minimal toxicity and have been demonstrated as effective in many tumors, 12 including CRC. 11,[13][14][15] Moreover, our previous studies demonstrated the feasibility and low toxicity of CIK cell treatment for several kinds of cancer, including hepatocellular carcinoma, 16 breast cancer, 17,18 epithelial ovarian cancer, 19 non-small-cell lung cancer 20 and nasopharyngeal carcinoma.…”