OK432-activated Natural Killer Cells Enhanced Trastuzumab (Herceptin®)-mediated Antibody-dependent Cellular Cytotoxicity in Patients with Advanced Cancer

Abstract

Background: Adoptive immunotherapy using natural killer (NK) cells from cancer patients yielded only modest success. Whether Herceptin® and OK432-activated NK cells (NK cells obtained by stimulating peripheral blood mononuclear cells with OK432 and interleukin-2) improve the outcome of adoptive immunotherapy against HER-2/neu positive tumor cells via antibody-dependent cellular cytotoxicity, was examined in vitro. Materials and Methods: A ⁵¹Cr release assay was performed to assess cytotoxicity. OK432-activated NK cells and lymphokine-activated killer (LAK) cells from healthy donors and cancer patients were used as effectors. Three cell lines expressing different amounts of HER-2/neu served as targets. Results: In the case of effectors from patients, OK432-activated NK cells showed higher cytotoxicity than that of LAK cells, and the cytotoxicity of OK432-activated NK cells against the SK-BR-3 cell line (over-expressing HER-2/neu) was increased by Herceptin®. Conclusion: Combination of Herceptin® and OK432-activeted NK cells may improve the efficacy of the treatment for HER-2/neu-positive malignancy.