Selective cytotoxicity and anticancer activity: ROS-induced cell death facilitated by metal complex

Abstract

Hepatocellular carcinoma (HCC) recurrence rate consists of 10%-20% and remains the leading cause of cancer-related death. We have successfully designed the protocol for adoptive immunotherapy to liver cirrhotic patients with HCC. In our study we have shown that activated lymphocytes, containing much of immune cells of innate immunity, from healthy volunteers, have a vigorous anticancer effect. However, the volume and viability for the treatment with activated lymphocytes might lead to limited effects. We aimed to develop a new therapeutic approach for the efficient expansion of such innate components of cellular immunity in combination with metal complex. Human lymphocytes were cultured for 7 days by appropriate protocol with cytokines. The phenotype and characterization of activated lymphocytes were identified by flow cytometric analysis and the cytotoxicity against tumor was determined. After being cultured for 7 days the proportion of cell fractions in the expanded activated lymphocytes varied among individuals. The average proportion of immune cells of innate immunity which were activated were in a high level. The addition of metal complex exhibits enhanced expression of surface receptors and intracellular cytokines which involved in antitumor process. Activated lymphocytes in combination with metal complex showed vigorous anticancer ability in vitro, of HepG2, an HCC cell line. These findings suggest that adoptive immunotherapy using activated lymphocytes might be a promising approach for inducing innate immunity to decrease the incidence of cancer recurrence and repeatedly applied in the clinical setting.