Advances in the development of personalized neoantigen-based therapeutic cancer vaccines.
Advances in the development of personalized neoantigen-based therapeutic cancer vaccines.
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DOI：
10.1038/s41571-020-00460-2
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Ott PA
中科院分区：
文献类型：
--
作者：
Blass E;Ott PA
在过去的十年里，随着各种免疫检查点抑制剂和嵌合抗原受体T细胞疗法在不同适应症中的开发和监管批准，免疫治疗领域彻底改变了许多癌症的治疗。另一种有希望的癌症免疫治疗方法涉及使用个性化疫苗，其设计用于触发针对新抗原的从头T细胞应答，所述新抗原对个体患者的肿瘤具有高度特异性，以扩增和拓宽肿瘤特异性T细胞的内源性库。通过快速和具有成本效益的测序和生物信息学技术的可用性，基于个性化新抗原的疫苗的初步临床研究结果已经证明了强大的肿瘤特异性免疫原性以及在黑色素瘤和其他癌症患者中抗肿瘤活性的初步证据。在本文中，我们概述了生成个性化新抗原疫苗所必需的复杂过程，回顾了肿瘤内发现的疫苗诱导T细胞的类型，并概述了增强T细胞反应的策略。此外，我们还讨论了在癌症患者中测试个性化新抗原疫苗的临床研究的现状，以及对这种新型的个性化免疫治疗方法未来临床研究的考虑。个性化的基于新抗原的治疗性疫苗有望成为癌症免疫疗法。本文综述了复杂的个性化新抗原疫苗的生产过程，疫苗诱导的T细胞反应和增强这些反应的策略。已完成的和正在进行的临床研究测试这样的疫苗进行了讨论，并考虑未来的临床研究，这种新型的，个性化的免疫疗法的形式进行了概述。基于新抗原的个体化治疗性癌症疫苗已被证明在黑素瘤和胶质母细胞瘤患者中是可行的、安全的和免疫原性的。不同的疫苗形式和递送策略目前正在涉及各种肿瘤类型患者的临床研究中进行测试。对疫苗诱导的新抗原特异性CD 4+和CD 8 + T细胞的表型、功能和持久记忆潜力进行更深入的评估，有助于提高对其治疗活性的理解，并优化疫苗接种策略。新抗原靶点发现正在不断推进，以改善可被CD 8 + T细胞识别的免疫原性新表位的鉴定;用于预测CD 4 + T细胞新表位的更具挑战性的任务的算法也正在出现。应进一步探索创新的疫苗输送平台和组合疗法的最有效时机，以降低成本和时间延迟，并提高临床疗效。
Within the past decade, the field of immunotherapy has revolutionized the treatment of many cancers with the development and regulatory approval of various immune-checkpoint inhibitors and chimeric antigen receptor T cell therapies in diverse indications. Another promising approach to cancer immunotherapy involves the use of personalized vaccines designed to trigger de novo T cell responses against neoantigens, which are highly specific to tumours of individual patients, in order to amplify and broaden the endogenous repertoire of tumour-specific T cells. Results from initial clinical studies of personalized neoantigen-based vaccines, enabled by the availability of rapid and cost-effective sequencing and bioinformatics technologies, have demonstrated robust tumour-specific immunogenicity and preliminary evidence of antitumour activity in patients with melanoma and other cancers. Herein, we provide an overview of the complex process that is necessary to generate a personalized neoantigen vaccine, review the types of vaccine-induced T cells that are found within tumours and outline strategies to enhance the T cell responses. In addition, we discuss the current status of clinical studies testing personalized neoantigen vaccines in patients with cancer and considerations for future clinical investigation of this novel, individualized approach to immunotherapy. Personalized neoantigen-based therapeutic vaccines hold promise as cancer immunotherapies. This Review provides an overview of the complex personalized neoantigen vaccine production process, vaccine-induced T cell responses and strategies to enhance these responses. Completed and ongoing clinical studies testing such vaccines are discussed, and considerations for future clinical investigation of this novel, individualized form of immunotherapy are outlined. Personalized therapeutic cancer vaccines predicated on neoantigens have been shown to be feasible, safe and immunogenic in patients with melanoma and glioblastoma. Different vaccine formats and delivery strategies are currently being tested in clinical studies involving patients with various tumour types. Deeper evaluation of the phenotypes, functionality and long-lasting memory potential of vaccine-induced neoantigen-specific CD4+ and CD8+ T cells is warranted to improve understanding of their therapeutic activity and optimize vaccination strategies. Neoantigen target discovery is continually being advanced to improve the identification of immunogenic neoepitopes that can be recognized by CD8+ T cells; algorithms for the more challenging task of predicting CD4+ T cell neoepitopes are also emerging. Innovative vaccine delivery platforms and the most effective timing of combinatorial therapies should be further explored to reduce costs and time delays and increase clinical efficacy.
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影响因子：
32.4
作者：
Abelin JG;Keskin DB;Sarkizova S;Hartigan CR;Zhang W;Sidney J;Stevens J;Lane W;Zhang GL;Eisenhaure TM;Clauser KR;Hacohen N;Rooney MS;Carr SA;Wu CJ
通讯作者：
Wu CJ
影响因子：
24.8
作者：
Ahmadzadeh, Mojgan;Pasetto, Anna;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
4.4
作者：
Bijker, Martijn S.;van den Eeden, Susan J. F.;van der Burg, Sjoerd H.
通讯作者：
van der Burg, Sjoerd H.
癌症免疫疗法。树突状细胞疫苗增加了黑色素瘤新抗原特异性T细胞的广度和多样性。
DOI：
10.1126/science.aaa3828
发表时间：
2015-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Carreno BM;Magrini V;Becker-Hapak M;Kaabinejadian S;Hundal J;Petti AA;Ly A;Lie WR;Hildebrand WH;Mardis ER;Linette GP
通讯作者：
Linette GP
DOI：
10.1084/jem.20180684
发表时间：
2018-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brummelman J;Mazza EMC;Alvisi G;Colombo FS;Grilli A;Mikulak J;Mavilio D;Alloisio M;Ferrari F;Lopci E;Novellis P;Veronesi G;Lugli E
通讯作者：
Lugli E