摘要
抗肿瘤单克隆抗体的高度特异性与杀伤细胞对肿瘤的细胞毒效应相互结合起来，是增强ＬＡＫ细胞抗肿瘤作用的重要途径。本研究用化学连接法制备了既可识别淋巴细胞表面ＣＤ３抗原又可识别ＬｉＢｒ黑素瘤细胞表面肿瘤相关抗原的双特异性抗体ＣＤ３－ＨＢ８７５９。ＦＡＣＳ分析证实，ＣＤ３－ＨＢ８７５９具有结合两种抗原的活性。４ｈ５１Ｃｒ释放细胞毒实验结果表明，ＣＤ３－ＨＢ８７５９在诱导相可显著增强ＬＡＫ对ＬｉＢｒ细胞的细胞毒效应，也能使非ＬＡＫ细胞获得细胞毒性；在杀伤相加入ＣＤ３－ＨＢ８７５９对ＬＡＫ细胞的细胞毒作用也具有促进作用。上述结果表明，ＣＤ３－ＨＢ８７５９是一种抗人黑素瘤的双特异性抗体，为体内应用提供了良好的实验基础。
CD3-melanoma bispecific antibodies (CD3-HB8759) were prepared by chemical conjugation of OKT3 with HB8759 McAb,which react with human melanoma cell line LiBr. Indirect immunofluorescence staining and flow cytometric analysis showed that CD3-HB8759 had dual specific activity to human PMBC and LiBt cells.The results of 51Cr release assay demonstrated that CD3HB8759 could promote the cytotoxicity of LAK cells against LiBr cells when added at the beginning of LAK-inducing culture with IL-2 or killing stage of the cytotoxic assay.In addition,PBMC could be induced to lyze LiBr cells by CD3-HB8759 without IL-2.These results indicated that CD3-HB8759 did augment the cytotoxicity of LAK cells against melanoma cell line LiBr,and the effect was performed by means of specific recognition and linkage of antigens expressed on the surface of effectors and targets by CD3-HB8759,suggesting that CD3-HB8759 bispecific antibody may be provided as a novel biologic agent foe treatment of melamoa.
