抗CD3-抗胶质瘤双特异抗体与IL-2协同的细胞毒性作用研究

Study on cooperative action of antiCD3×antiglioma bispecific antibody and IL2 on cytotoxicity of LAK cells

目的：探索提高胶质瘤治疗效果的新方法。方法：以化学偶联制备抗ＣＤ３－抗胶质瘤双特异性抗体，以３Ｈ掺入法测定其与ＩＬ－２协同增强ＬＡＫ细胞对胶质瘤的细胞毒性，以ＣＤ３单抗、胶质瘤单抗、二种单抗混和物及ＲＰＭＩ１６４０作对照。结果：双特异抗体与单抗相比，能显著提高ＬＡＫ细胞对胶质瘤细胞的杀伤作用；双抗加入ＩＬ－２后，ＬＡＫ细胞毒性得到显著的提高，ＩＬ－２也能增强抗ＣＤ３单抗和ＳＺ３９单抗的细胞毒性；同时发现，来源于恶性胶质瘤患者的ＬＡＫ细胞毒性，在加入单抗、双抗和ＩＬ－２后，其细胞毒性与正常人相比，仍有显著性差异。

Objective: To investigate a new method for improving the therapeutic effect on glioma. Method: The antiCD3×antiglioma bispecific antibody (BIAB) was built by chemical conjugating method. Cytotoxicity of LAK cells against glioma cells enhanced by the BIAB and IL2 was examined with3H incorporation method, comparing with control groups: CD3 antibody, antiglioma antibody SZ39, mixture of the two antibodies, RPMI 1640. Results: Cytotoxicity of LAK cells against glioma cells could be markedly enhanced by BIAB compared with antiCD3 and SZ39 monoclonal antibody (P<001 or P<005). When LAK cells incubating with IL2, its cytotoxicity enhanced by BIAB was more high (P<005). Also, we found that cytotoxicty of LAK cells from patients with malignant glioma was lower than that from normal individuals when incubating with antiCD3 and SZ39 monoclonal antibody, BIAB or IL2(P<005,or P<001). Conclusion: AntiCD3×anti glioma BIAB could markedly enhance the cytotoxicity of LAK cells against glioma.