Hattori K, Tsukamoto H, Ohta S, Yabe M, Yabe H, Kato S, Takakura I, Ueda R, Habu S, Nishimura T
Department of Pediatrics, Tokai University School of Medicine, Isehara, Japan.
Bone Marrow Transplant. 1995 Feb;15(2):193-8.
The F(ab')2 bispecific antibody (BSAb) was prepared from anti-CD3 moAb and anti-CD10 moAb. The BSAb could react with both CD3+ T cells and CD10+ leukemia cells and triggered T cell-mediated cytotoxicity. To apply the BSAb to prevention of leukemic relapse after BMT, we investigated the generation of both CD4+ and CD8+ anti-tumor effector T cells from patient's PBMC 14 days after BMT. Neither CD4+ T cells nor CD8+ T cells, which were activated with immobilized anti-CD3 moAb plus IL-2, could lyse CD10+ leukemia cells by themselves, but they showed augmented cytotoxicity against CD10+ leukemia cells by targeting with anti-CD3 x anti-CD10 BSAb. Moreover, the activated CD4+ T cells were demonstrated to produce IL-2 and IFN-gamma when they were cultured with CD10+ leukemia cells in the presence of the BSAb. The BSAb-mediated cytotoxicity of activated T cells was demonstrated not only against the recipient leukemia cells but also against third party leukemia cells. These results suggested that anti-CD3 x anti-CD10 BSAb might be a good tool to prevent relapse after BMT in combination with activated CD4+ T cells and CD8+ T cells.
F(ab')2双特异性抗体（BSAb）由抗CD3单克隆抗体和抗CD10单克隆抗体制备而成。该BSAb可与CD3+ T细胞和CD10+白血病细胞发生反应，并引发T细胞介导的细胞毒性。为了将该BSAb应用于预防异基因骨髓移植（BMT）后白血病复发，我们研究了BMT后14天患者外周血单个核细胞（PBMC）中CD4+和CD8+抗肿瘤效应T细胞的产生情况。单独用固定化抗CD3单克隆抗体加白细胞介素-2激活的CD4+ T细胞和CD8+ T细胞自身均不能裂解CD10+白血病细胞，但通过抗CD3×抗CD10 BSAb靶向作用，它们对CD10+白血病细胞的细胞毒性增强。此外，当在BSAb存在的情况下，将激活的CD4+ T细胞与CD10+白血病细胞共培养时，证实其可产生白细胞介素-2和γ干扰素。激活的T细胞经BSAb介导的细胞毒性不仅针对受体白血病细胞，也针对第三方白血病细胞。这些结果表明，抗CD3×抗CD10 BSAb可能是联合激活的CD4+ T细胞和CD8+ T细胞预防BMT后复发的良好工具。
