Strategies to use immune modulators in therapeutic vaccines against cancer.
Strategies to use immune modulators in therapeutic vaccines against cancer.
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DOI：
10.1053/j.seminoncol.2012.02.002
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发表时间：
2012-06
影响因子：
4
通讯作者：
Wood LV
中科院分区：
文献类型：
--
作者：
Berzofsky JA;Terabe M;Wood LV
癌症与自身如此相似，以至于免疫系统很难消除它们，而那些已经逃脱了自然免疫监控的癌症已经越过了自然的免疫屏障，变成了恶性肿瘤。一种成功的治疗性癌症疫苗必须克服这些逃逸机制。我们的实验室专注于一种多步骤的“推-拉”方法，在这种方法中，我们结合各种策略来克服每一种逃逸机制。如果肿瘤表位不具有足够的免疫原性，我们可以通过表位增强来提高其免疫原性，从而改善其与主要组织相容性复合体(MHC)分子的结合亲和力。如果抗肿瘤反应太弱或表型错误，我们使用细胞因子、共刺激分子、Toll样受体配体和其他分子佐剂不仅增加反应的数量，而且增加反应的质量，将反应推向正确的方向。最后，肿瘤需要多种免疫抑制机制来保护自己，所以我们也需要克服这些机制，包括阻断或耗尽调节细胞或抑制调节分子，以通过移除刹车来拉动反应。其中一些单独的策略现在已经转化为癌症患者的人体临床试验。在推拉方法中，这些方法的组合对于成功的癌症免疫治疗是有希望的。
Cancers so much resemble self that they prove difficult for the immune system to eliminate, and those that have already escaped natural immunosurveillance have gotten past the natural immune barriers to malignancy. A successful therapeutic cancer vaccine must overcome these escape mechanisms. Our laboratory has focused on a multistep “push-pull” approach in which we combine strategies to overcome each of the mechanisms of escape. If tumor epitopes are insufficiently immunogenic, we increase their immunogenicity by epitope enhancement, improving their binding affinity to major histocompatibility complex (MHC) molecules. If the anti-tumor response is too weak or of the wrong phenotype, we use cytokines, costimulatory molecules, Toll-like receptor ligands, and other molecular adjuvants to increase not only the quantity of the response, but also its quality, to push the response in the right direction. Finally, the tumor invokes multiple immunosuppressive mechanisms to defend itself, so we need to overcome those as well, including blocking or depleting regulatory cells or inhibiting regulatory molecules, to pull the response by removing the brakes. Some of these strategies individually have now been translated into human clinical trials in cancer patients. Combinations of these in a push-pull approach are promising for the successful immunotherapy of cancer.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
DOI：
10.1073/pnas.94.20.10856
发表时间：
1997-09-30
影响因子：
11.1
作者：
Ahlers, JD;Takeshita, T;Berzofsky, JA
通讯作者：
Berzofsky, JA
影响因子：
4.4
作者：
Ahlers, JD;Belyakov, IM;Berzofsky, JA
通讯作者：
Berzofsky, JA
影响因子：
8.4
作者：
Bueno, Lorea;de Alwis, Dinesh P.;Troconiz, Inaki F.
通讯作者：
Troconiz, Inaki F.
影响因子：
32.4
作者：
ALEXANDER, J;SIDNEY, J;GREY, HM
通讯作者：
GREY, HM