超级抗原在肿瘤免疫治疗中的应用

The Application of Superantigen in Tumor Immunotherapy

超级抗原(Superantigen,SAg)作为一种优秀的免疫激活剂,通过诱导T细胞的活化来增强机体抗肿瘤免疫反应,可能是未来肿瘤免疫治疗的新希望。“超级抗原”一词在1989年被首次提出,用来描述细菌毒素对免疫系统的高效刺激特性。金黄色葡萄球菌能产生约20种不同类型的金黄色葡萄球菌肠毒素(Staphylococcal enterotoxins,SEs),这类蛋白质抗原是典型的细菌超级抗原,是一种能够在极低浓度下即可有效刺激细胞毒性T淋巴细胞活性和促进细胞因子产生的诱导剂。超级抗原通过与抗原呈递细胞(APCs)上的主要组织相容性复合体II(MHC-II)的外沟和T细胞受体(Tcr)的特异性Vβ区交叉结合,直接激活T淋巴细胞,使含有TCR Vβ结构域的T细胞进行超表达,使免疫细胞释放大量的抗肿瘤细胞因子和其他效应分子。基于免疫细胞具有识别自我和非我的特点,超级抗原利用人体自身免疫系统杀死肿瘤细胞,因此在肿瘤免疫治疗领域具有巨大应用潜力。对超级抗原的生物活性特征、临床抗肿瘤效果、药物开发策略等多方面进行简要综述,并对其未来应用前景加以展望。对超级抗原的作用机理及临床应用的深入研究,将有助于肿瘤免疫治疗的发展,从而使通过T淋巴细胞干预治疗恶性肿瘤成为可能。

Superantigen(SAg),as an excellent immune activator,enhances the anti-tumor immune response by inducing the activation of T cells,which may be a new approach for tumor immunotherapy in the future.The term"superantigen"was first proposed in 1989 to describe those bacterial toxins with highly effectiveness of stimulating immune system.Staphylococcus aureus can produce about 20 different types of Staphylococcal enterotoxins(SEs).This type of protein antigen is a typical bacterial superantigen,which can effectively activate cytotoxic T lymphocytes even at low concentrations leading to massive releasing of cytokines.Superantigens directly activate T lymphocytes by cross-binding with the outer groove of the major histocompatibility complex II(MHC-II)on antigen presenting cells(APCs)and the specific Vβ region of the T cell receptor(Tcr).Overexpression of T cells containing TCR Vβdomain allows producing a large amount of anti-tumor effector molecules.Based on the self-recognition characteristics of immune cells,superantigens propel the immune system to kill tumor cells,so it has great application potential in the field of tumor immunotherapy.This article briefly reviews the biological activity characteristics,anti-tumor effects in clinic,and drug development strategies of superantigens,and prospects its future applications.In-depth research on the mechanism and clinical applications of superantigens will help the development of tumor immunotherapy,thereby making it possible to treat malignant tumors through T lymphocyte intervention.