癌症治疗的肽基疫苗。
Peptide-based vaccine for cancer therapies.
发表日期:2023
作者:
Luigi Buonaguro, Maria Tagliamonte
来源:
Disease Models & Mechanisms
摘要:
肿瘤治疗上可采用基于肽的不同策略,特别是用于抑制肿瘤生长和疾病复发的进展。在过去的十年中,在抗肿瘤治疗策略的背景下,通过不同的肿瘤模型已对基于肽的疫苗进行了评估。用于癌症疫苗开发的肽可分为两类:肿瘤相关抗原(TAAs)和肿瘤特异性抗原(TSAs),这些肽由抗原递呈细胞(APCs)捕获、内化、处理并呈现给细胞免疫。负载在MHC I类上的肽可通过特定的CD8+ T细胞TCR识别,激活这些细胞以对呈现相同肽-MHC I复合物的肿瘤细胞产生细胞毒作用。此过程被定义为主动免疫疗法,因为宿主的免疫系统要么是新生激活的,要么是重新刺激的,以产生有效的、针对肿瘤特异的免疫反应,最终可能导致肿瘤的退化。然而,虽然临床前数据经常显示出令人鼓舞的结果,但目前为止,包括基于肽的治疗性癌症疫苗在内的临床试验并未提供满意的数据。基于肽的癌症疫苗的有限功效是由多个因素引起的,包括特定靶肿瘤抗原的鉴定、肽的有限免疫原性以及高度免疫抑制的肿瘤微环境(TME)。只有解决所有这些不同方面,才能开发出有效的癌症疫苗。本综述描述了各个因素的最新状态。版权所有 2023 Buonaguro 和 Tagliamonte。
Different strategies based on peptides are available for cancer treatment, in particular to counter-act the progression of tumor growth and disease relapse. In the last decade, in the context of therapeutic strategies against cancer, peptide-based vaccines have been evaluated in different tumor models. The peptides selected for cancer vaccine development can be classified in two main type: tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs), which are captured, internalized, processed and presented by antigen-presenting cells (APCs) to cell-mediated immunity. Peptides loaded onto MHC class I are recognized by a specific TCR of CD8+ T cells, which are activated to exert their cytotoxic activity against tumor cells presenting the same peptide-MHC-I complex. This process is defined as active immunotherapy as the host's immune system is either de novo activated or restimulated to mount an effective, tumor-specific immune reaction that may ultimately lead to tu-mor regression. However, while the preclinical data have frequently shown encouraging results, therapeutic cancer vaccines clinical trials, including those based on peptides have not provided satisfactory data to date. The limited efficacy of peptide-based cancer vaccines is the consequence of several factors, including the identification of specific target tumor antigens, the limited immunogenicity of peptides and the highly immunosuppressive tumor microenvironment (TME). An effective cancer vaccine can be developed only by addressing all such different aspects. The present review describes the state of the art for each of such factors.Copyright © 2023 Buonaguro and Tagliamonte.