Kalland T, Dohlsten M, Abrahmsén L, Hedlund G, Björk P, Lando P A, Sundstedt A, Akerblom E, Lind P
Kabi Pharmacia Oncology, Lund, Sweden.
Cell Biophys. 1993 Jan-Jun;22(1-3):147-64. doi: 10.1007/BF03033872.
The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on MHC class II antigens. In order to induce T lymphocytes to reject a tumor, we substituted the specificity of SEA for MHC class II molecules with specificity for tumor cells by combining SEA with a MAb recognizing colon carcinomas. Chemical conjugates or recombinant fusion proteins of the MAb C215 and SEA retained excellent antigen binding properties whereas the binding to MHC class II was markedly reduced. The hybrid proteins directed SEA responsive T cells to tumors with specificity determined by the specificity of the MAb. Significant tumor cell killing was obtained at picomolar concentrations of the hybrid proteins and was the result of direct cell mediated by cytotoxicity as well as production of tumoricidal cytokines by T cells. Targeting of superantigens represents a novel approach to specific immunomodulation and deserves further study as a potential therapy for malignant disease.
细菌超抗原葡萄球菌肠毒素A（SEA）在与II类主要组织相容性复合体（MHC）抗原结合时，是T淋巴细胞的一种极其有效的激活剂。为了诱导T淋巴细胞排斥肿瘤，我们通过将SEA与一种识别结肠癌的单克隆抗体（MAb）相结合，用对肿瘤细胞的特异性取代了SEA对II类MHC分子的特异性。MAb C215与SEA的化学偶联物或重组融合蛋白保留了优异的抗原结合特性，而与II类MHC的结合则显著减少。这些杂交蛋白将对SEA有反应的T细胞导向肿瘤，其特异性由MAb的特异性决定。在皮摩尔浓度的杂交蛋白作用下可实现显著的肿瘤细胞杀伤，这是细胞毒性介导的直接细胞作用以及T细胞产生杀肿瘤细胞因子的结果。将超抗原靶向作为一种特异性免疫调节的新方法，作为恶性疾病的潜在治疗方法值得进一步研究。
