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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Gene-based vaccines and immunotherapeutics
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Gene-based vaccines and immunotherapeutics

机译：基于基因的疫苗和免疫治疗

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DNA vaccines, comprised of plasmid DNA encoding proteins from pathogens, allergens, and tumors, are being evaluated as prophylactic vaccines and therapeutic treatments for infectious diseases, allergies, and cancer; plasmids encoding normal human proteins are likewise being tested as vaccines and treatments for autoimmune diseases. Examples of in vivo prophylaxis and immunother-apy, based on different types of immune responses (humoral and cellular), in a variety of disease models and under evaluation in early phase human clinical trials are presented. Viral vectors continue to show better levels of expression than those achieved by DNA plasmid vectors. We have focused our clinical efforts, at this time, on the use of recombinant viral vectors for both vaccine as well as cytokine gene transfer studies. We currently have four clinical programs in cancer immunotherapy. Two nonspecific im-munotherapy programs are underway that apply adenoviral vectors for the transfer of cytokine genes into tumors in situ. An adenovirus-IFNγ construct (TG1042) is currently being tested in phase Ⅱ clinical trials in cutaneous lymphoma. A similar construct, adenovirus-IL2 (TG1024), also injected directly into solid tumors, is currently being tested in patients with solid tumors (about one-half of which are melanoma). Encouraging results are seen in both programs. Two cancer vaccine immunotherapy programs focus on two cancer-associated antigens: human papilloma virus E6 and E7 proteins and the epithelial cancer-associated antigen MUC1. Both are encoded by a highly attenuated vaccinia virus vector [modified vaccinia Ankara (MVA)] and both are coexpressed with IL-2. Encouraging results seen in both of these programs are described.
机译：DNA疫苗由编码来自​​病原体，过敏原和肿瘤的蛋白质的质粒DNA组成，目前正在被评估为传染性疾病，过敏和癌症的预防性疫苗和治疗方法。同样，编码正常人蛋白质的质粒也正在作为自身免疫性疾病的疫苗和治疗方法进行测试。提出了基于各种类型免疫反应（体液和细胞）的体内预防和免疫疗法的实例，这些实例在多种疾病模型中进行了早期人类临床试验的评估。病毒载体继续表现出比DNA质粒载体更好的表达水平。目前，我们将临床工作的重点放在了将重组病毒载体用于疫苗以及细胞因子基因转移研究上。我们目前在癌症免疫治疗方面有四个临床计划。正在实施两个非特异性免疫疗法计划，这些计划应用腺病毒载体将细胞因子基因原位转移到肿瘤中。腺病毒-IFNγ构建体（TG1042）目前正在皮肤淋巴瘤的Ⅱ期临床试验中进行测试。也正在直接注射到实体瘤中的类似构建体腺病毒-IL2（TG1024），也正在实体瘤患者中进行测试（其中约有一半是黑色素瘤）。在两个程序中都可以看到令人鼓舞的结果。两项癌症疫苗免疫疗法计划着眼于两种与癌症相关的抗原：人乳头瘤病毒E6和E7蛋白以及与上皮癌相关的抗原MUC1。两者均由高度减毒的牛痘病毒载体[修饰的牛痘安卡拉（MVA）]编码，并且均与IL-2共表达。描述了在这两个程序中看到的令人鼓舞的结果。

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