Sudo Toshimi, Aruga Atsushi, Shimizu Koichi, Matsushita Norimasa, Takasaki Ken
Department of Gastrointerological Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Anticancer Res. 2006 Nov-Dec;26(6B):4327-33.
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.
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.
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.
Combination of Herceptin and OK432-activeted NK cells may improve the efficacy of the treatment for HER-2/neu-positive malignancy.
采用癌症患者的自然杀伤（NK）细胞进行过继性免疫治疗仅取得了一定程度的成功。本研究在体外检测了赫赛汀和OK432激活的NK细胞（通过用OK432和白细胞介素-2刺激外周血单个核细胞获得的NK细胞）是否能通过抗体依赖性细胞毒性作用改善针对HER-2/neu阳性肿瘤细胞的过继性免疫治疗效果。
采用51Cr释放试验评估细胞毒性。将来自健康供体和癌症患者的OK432激活的NK细胞和淋巴因子激活的杀伤（LAK）细胞用作效应细胞。使用三种表达不同量HER-2/neu的细胞系作为靶细胞。
在患者来源的效应细胞中，OK432激活的NK细胞比LAK细胞表现出更高的细胞毒性，并且赫赛汀可增强OK432激活的NK细胞对SK-BR-3细胞系（HER-2/neu过表达）的细胞毒性。
赫赛汀与OK432激活的NK细胞联合使用可能会提高HER-2/neu阳性恶性肿瘤的治疗效果。
