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近年来,肿瘤免疫治疗取得了令人瞩目的重大突破,采用过继免疫技术输入工程抗体或工程效应T细胞,一些接受治疗的患者获得持久的缓解甚至痊愈.然而,这些单靶点治疗技术对部分患者没有疗效.有证据表明,肿瘤的异质性(heterogeneity)和不断进化(evolving)的特性是造成治疗失败的原因,只有发展出针对这些肿瘤特性的新方法,才能实现新的突破.本文提出用合成免疫策略(synthetic immunity,SI)来实现这一目标.SI的原则是通过制备一组工程抗体和抗体重新定向的细胞毒T淋巴细胞(antibody-retargeted cytotoxic T cells)高度特异性地杀死全部肿瘤细胞系而达到根治的目的.要实现这一目标,只能通过系统化方法来选择组合工程抗体,具体是建立一个肿瘤抗原系统树(tumor epitope-tree)来确定肿瘤细胞系及其抗原的系统构成,然后选择“树干或主要分杈”上的“抗原靶点组”来进行过继免疫治疗,最终消灭所有肿瘤细胞系.同时结合其他技术如扩大抗原表位数量、提高抗体亲和力和T细胞活性等,可以进一步提高SI的效率.此外,用非病毒DNA基因载体在体内生产工程抗体将是一个安全、有效和经济的解决方案.
In recent years, tumor immunotherapy has made remarkable breakthroughs, the use of adoptive immunization technology imported engineering antibodies or engineered effector T cells, some patients receiving treatment for sustained remission or even cure.However, these single-target therapy for part of There is no evidence of efficacy and there is evidence that tumor heterogeneity and evolving properties are the cause of treatment failure and that new breakthroughs can only be achieved by developing new approaches to these tumor properties.This paper presents This goal is achieved with synthetic immunity (SI), the principle of which is highly specific killing by preparing a set of engineered antibodies and antibody-retargeted cytotoxic T cells All tumor cell lines to achieve the purpose of radicalization.To achieve this goal, only through a systematic approach to select a combination of engineering antibodies, specifically to establish a tumor antigen-tree (tumor epitope-tree) to determine the tumor cell lines and their antigens , And then select the “target group ” on the “trunk or main branch ” to carry out adoptive immunotherapy , Eventually eliminating all tumor cell lines, while further enhancing the efficiency of SI in combination with other techniques such as expanding the number of epitopes, increasing antibody affinity and T cell activity, etc. In addition, in vivo production of engineered antibodies with non-viral DNA gene vectors will be A safe, effective and economical solution.