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

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancer. HCC is the second highest mortality rate out of all major malignant carcinomas worldwide. Objectives: The aims of this study were to establish a rapid and easily handled culture method for sufficient expansion of viable and cytotoxic cytokine-induced killer (CIK) cells against HCC. Also, this study aimed to examine the morphologic, phenotypic, and functional characteristics of CIK cells. Method: Peripheral blood mononuclear cells (PBMCs) were cultured in a preliminary static culture to remove adherent cells. The suspended cells were cultured for 14 days with interferon-γ, human monoclonal anti-CD3 antibody and interleukin-2. Aliquots of induced PBMCs were harvested weekly to assess informative morphologic and phenotypic features of CIK cells. Mature CIK cells were subjected to functional assays that included the production of TNFα and the cytotoxic effect on HCC cell line, HepG2. Findings: CIK cells could be successfully expanded from all samples with a significant increase in T cells, natural killer cells, and natural killer T cells. TNFα concentration in the culture supernatant was significantly increased. The cytotoxic effect of CIK cells on HepG2 cells was nearly 60% at 40:1, effector: target ratio. Regression analysis was used to predict the CIK: HepG2 ratio required to achieve complete cytotoxicity. Conclusion: This study provides a detailed and simple strategy for culturing effective CIK cells. Mature CIK cells showed a high functional capacity against HCC; which will support the further ongoing practice of immunotherapy integration into different current cancer treatment protocols.