Gustave Roussy; Villejuif, France ; INSERM, U848; Villejuif, France ; Université Paris-Sud/Paris XI; Le Kremlin-Bicêtre, France ; Equipe 11 labellisée par la Lique Nationale contre le Cancer; Centre de Recherche des Cordeliers; Paris, France.
Gustave Roussy; Villejuif, France.
Oncoimmunology. 2013 Dec 1;2(12):e26621. doi: 10.4161/onci.26621. Epub 2013 Nov 4.
Throughout the past 3 decades, along with the recognition that the immune system not only influences oncogenesis and tumor progression, but also determines how established neoplastic lesions respond therapy, renovated enthusiasm has gathered around the possibility of using vaccines as anticancer agents. Such an enthusiasm quickly tempered when it became clear that anticancer vaccines would have to be devised as therapeutic, rather than prophylactic, measures, and that malignant cells often fail to elicit (or actively suppress) innate and adaptive immune responses. Nonetheless, accumulating evidence indicates that a variety of anticancer vaccines, including cell-based, DNA-based, and purified component-based preparations, are capable of circumventing the poorly immunogenic and highly immunosuppressive nature of most tumors and elicit (at least under some circumstances) therapeutically relevant immune responses. Great efforts are currently being devoted to the identification of strategies that may provide anticancer vaccines with the capacity of breaking immunological tolerance and eliciting tumor-associated antigen-specific immunity in a majority of patients. In this sense, promising results have been obtained by combining anticancer vaccines with a relatively varied panels of adjuvants, including multiple immunostimulatory cytokines, Toll-like receptor agonists as well as inhibitors of immune checkpoints. One year ago, in the December issue of , we discussed the biological mechanisms that underlie the antineoplastic effects of peptide-based vaccines and presented an abundant literature demonstrating the prominent clinical potential of such an approach. Here, we review the latest developments in this exciting area of research, focusing on high-profile studies that have been published during the last 13 mo and clinical trials launched in the same period to evaluate purified peptides or full-length proteins as therapeutic anticancer agents.
在过去的 30 年中,人们逐渐认识到免疫系统不仅影响肿瘤的发生和肿瘤的进展,而且还决定了已建立的肿瘤病变对治疗的反应,这使得人们对将疫苗作为抗癌药物的可能性重新产生了兴趣。当人们清楚地认识到抗癌疫苗必须作为治疗而非预防措施来设计,并且恶性细胞经常不能引发(或主动抑制)先天和适应性免疫反应时,这种热情很快就消退了。尽管如此,越来越多的证据表明,包括基于细胞的、基于 DNA 的和基于纯化成分的制剂在内的多种抗癌疫苗能够克服大多数肿瘤的免疫原性差和高度免疫抑制的性质,并引发(至少在某些情况下)具有治疗相关性的免疫反应。目前正在努力寻找策略,使抗癌疫苗能够打破免疫耐受,并在大多数患者中引发肿瘤相关抗原特异性免疫。在这方面,通过将抗癌疫苗与多种佐剂(包括多种免疫刺激细胞因子、Toll 样受体激动剂以及免疫检查点抑制剂)联合使用,已经取得了有希望的结果。一年前,在 12 月的那一期《癌症免疫学研究》中,我们讨论了基于肽的疫苗的抗肿瘤作用的生物学机制,并介绍了大量文献,证明了这种方法具有突出的临床潜力。在这里,我们回顾了这一令人兴奋的研究领域的最新进展,重点介绍了过去 13 个月发表的备受瞩目的研究以及同期启动的临床试验,以评估纯化肽或全长蛋白作为治疗性抗癌药物。