双功能抗体介导的胃癌杀伤效应

The Cytotoxic Effect on Gastric Cancer Cells Mediated by Bispecific Monoclonal antibody

将诱变的αＣＤ３杂交瘤（ＴＫ~－）与ＰＤ４杂交瘤（ＨＧＰＲＴ~－）融合，获得分泌双功能抗体（ＢｓＡｂ）的四体杂交瘤Ｃ３．ＢｓＡｂＣ３可分别与ＣＤ３分子及胃癌相关抗原Ｐ４０反应．体外杀伤试验证实，当效靶比为４０：１，ＢｓＡｂＣ３浓度为１ｍｇ／Ｌ时，其杀伤效应可达７７．６％．该杀伤效应具有明显的特异性，仅Ｐ４０阳性表达的靶细胞可被溶解，体内杀伤试验证实，裸鼠接种胃癌细胞后５ｄ，以ＢｓＡｂＣ３活化的外周血淋巴细胞（ＰＢＬｓ）经局部皮下注射处理，可使移植胃癌完全消退（５／５）．这一明显的治疗作用可能与局部注射途径有关，可供临床应用参考．

A bispecific monoclonal antibody (BsAb) C3 was obtained by fusing α CD3 hybridoma (TK￣- ) with PD4 hybridorna (HGPRT￣-) ,a cell line which secrets monoclonal antibody (McAb)against gastric cancer-associated antigen P40. When the ratio of peripheral blood lymphocytes (PBLs) to target cells was 40 : 1,and the concentration of BsAb was 1 mg/L ,the cytotoxicity in vitro could reach 77. 6 %,and it was so specific,that only P40 positive target cells were lysed. Five days after inoculation,the gastric cancer bearing nude mice were treated with subcutaneous injection of BsAb C3 and PBLs around inoculation sites. On the 50th day after inoculation,all the tumors (5/5) in the treated group disappeared. This phenomena was confirmed by histopathological examinations,and the significant effect might be contributed to the local infusion approach.