Is It Possible to Develop Cancer Vaccines to Neoantigens, What Are the Major Challenges, and How Can These Be Overcome? Neoantigens: Nothing New in Spite of the Name
Is It Possible to Develop Cancer Vaccines to Neoantigens, What Are the Major Challenges, and How Can These Be Overcome? Neoantigens: Nothing New in Spite of the Name
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DOI：
10.1101/cshperspect.a028829
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发表时间：
2018-11-01
影响因子：
7.2
通讯作者：
Rammensee, Hans-Georg
中科院分区：
文献类型：
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作者：
Finn, Olivera J.;Rammensee, Hans-Georg
“新抗原”这个术语，用来指肿瘤细胞上新表达的分子，由来已久。100多年前，罗斯在鸡身上发现了一种致癌病毒，这一开创性的发现，以及随后在动物身上发现的其他致癌病毒，表明了人类癌症的病毒病因学。在20世纪60年代和70年代对其他致癌病毒的研究导致了爱泼斯坦-巴尔病毒(EBV)、乙肝病毒(HBV)和人乳头瘤病毒(HPV)的发现，并一直持续到现在。与此同时，方兴未艾的免疫学领域提出了这样一个问题：动物或人类的免疫系统能否识别从自身组织发展而来的肿瘤，以及哪些类型的抗原可以将肿瘤与正常细胞区分开来。致癌病毒编码的分子提供了最符合逻辑的候选分子，并迅速收集了体液和细胞识别病毒抗原的证据，这些新抗原被称为新抗原。然而，对携带病毒的肿瘤的血清学反应通常会显示与病毒蛋白无关的新抗原，并在多种肿瘤类型上表达，这预示着后来发现的肿瘤细胞中其他基因的多重变化产生了非病毒新抗原。
The term "neoantigen," as applied to molecules newly expressed on tumor cells, has a long history. The groundbreaking discovery of a cancer causing virus in chickens by Rous over 100 years ago, followed by discoveries of other tumor-causing viruses in animals, suggested a viral etiology of human cancers. The search for other oncogenic viruses in the 1960s and 1970s resulted in the discoveries of Epstein-Barr virus (EBV), hepatitis B virus (HBV), and human papilloma virus (HPV), and continues until the present time. Contemporaneously, the budding field of immunology was posing the question can the immune system of animals or humans recognize a tumor that develops from one's own tissues and what types of antigens would distinguish the tumor from normal cells. Molecules encoded by oncogenic viruses provided the most logical candidates and evidence was quickly gathered for both humoral and cellular recognition of viral antigens, referred to as neoantigens. Often, however, serologic responses to virus-bearing tumors revealed neoantigens unrelated toviral proteins and expressed onmultiple tumor types, foreshadowing later findings of multiple changes in other genes in tumor cells creating nonviral neoantigens.