Suicide gene-modified killer cells as an allogeneic alternative to autologous cytokine-induced killer cell immunotherapy of hepatocellular carcinoma

Adoptive immunotherapy using autologous cytokine-induced killer (CIK) cells reduces the recurrence rate of hepatocellular carcinoma (HCC) in association with transarterial chemoembolization or radiofrequency. However, a large-scale development of this immunotherapy remains difficult to consider in an autologous setting, considering the logistical hurdles associated with the production of this cell therapy product. A previous study has provided the in vitro and in vivo proof-of-concept that allogeneic suicide gene-modified killer cells (aSGMKCs) from healthy blood donors (a cell therapy product previously demonstrated to provide anti-leukemic effects to patients receiving allogeneic hematopoietic transplantation) may exert a potent anti-tumor effect towards HCC. Therefore, the development of a bank of `ready-for-use' aSGMKCs was proposed as an approach allowing for the development of immunotherapies that are more convenient and on a broader scale than that of autologous therapies. In the present study, aSGMKCs were compared with CIK cells generated according to three different protocols. Similar to CIK cells, the cytotoxic activity of aSGMKCs toward the Huh-7 HCC cell line was mediated by tumor necrosis factor-related apoptosis-inducing ligand, tumor necrosis factor- and interferon-. Furthermore, the frequency of natural killer (NK), NK-like T and T cells, and their in vitro and in vivo cytotoxicity activities were similar between aSGMKCs and CIK cells. Thus, the present study demonstrated that aSGMKCs are similar to CIK cells, further suggesting the possibility for future use of aSGMKCs in the treatment of solid tumors, including HCC.