Nishimura T, Nakamura Y, Tsukamoto H, Takeuchi Y, Tokuda Y, Iwasawa M, Yamamoto T, Masuko T, Hashimoto Y, Habu S
Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Int J Cancer. 1992 Mar 12;50(5):800-4. doi: 10.1002/ijc.2910500523.
To develop an efficient strategy for the targeting of anti-tumor effector cells, we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2 proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2-positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from peripheral-blood mononuclear cells by activation with immobilized anti-CD3 monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb caused the induction of specific cytotoxicity against c-erbB-2-positive tumor cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb. Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer cells implanted in nude mice. Our results strongly suggest that the c-erbB-2 proto-oncogene product on human tumor cells may be a good target for BsAb-directed adoptive tumor immunotherapy.
为了开发一种靶向抗肿瘤效应细胞的有效策略，我们制备了含有抗CD3和抗c-erbB-2原癌基因产物的双特异性抗体（BsAb）。所制备的BsAb能与c-erbB-2阳性肿瘤细胞和CD3+CTL特异性反应。通过用固定化抗CD3单克隆抗体（MAb）加IL-2激活从外周血单核细胞诱导产生的人CD4+辅助/杀伤性T细胞，对肿瘤细胞无明显细胞毒性。然而，用BsAb处理人CD4+辅助/杀伤性细胞可诱导其对c-erbB-2阳性肿瘤细胞产生特异性细胞毒性。在BsAb存在的情况下，CD4+辅助/杀伤性细胞在与c-erbB-2阳性肿瘤细胞共培养期间也产生大量IL-2。此外，与BsAb联合使用时，CD4+辅助/杀伤性细胞对植入裸鼠体内的c-erbB-2转染细胞或人结肠癌细胞显示出强大的体内抗肿瘤作用。我们的结果强烈表明，人肿瘤细胞上的c-erbB-2原癌基因产物可能是BsAb介导的过继性肿瘤免疫治疗的良好靶点。
