Improving T cell responses to modified peptides in tumor vaccines.
Improving T cell responses to modified peptides in tumor vaccines.
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DOI：
10.1007/s12026-012-8348-9
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发表时间：
2013-03
影响因子：
4.4
通讯作者：
Slansky, Jill E.
中科院分区：
文献类型：
--
作者：
Buhrman, Jonathan D.;Slansky, Jill E.
免疫识别和消除癌细胞是癌症免疫治疗的主要目标。然而，包括免疫耐受和肿瘤诱导的免疫抑制在内的障碍往往限制了有益的免疫反应。疫苗接种是一种建议的干预措施，可能有助于克服这些问题，是癌症免疫治疗研究的一个活跃领域。用肿瘤抗原肽进行免疫是一种很有前途的、直接的疫苗策略，可以增强预先存在的抗肿瘤免疫。然而，肿瘤抗原往往是弱的T细胞激动剂，这可归因于多种机制，包括免疫自身耐受性和自身来源的肿瘤肽的免疫原性差。克服这些机制的一种策略是接种mimotopes，或肿瘤抗原的肽模拟物，它改变抗原呈递和/或T细胞活化，以增加肿瘤特异性T细胞的扩增。对mimotope疫苗策略的评估表明，即使肽序列的细微改变也能显著改变抗原呈递和T细胞受体识别。大多数研究都是使用T细胞克隆进行的，这可能不是自然发生的抗肿瘤反应的准确代表。在多克隆T细胞库和多克隆疫苗接种后产生的克隆之间的关系尚不清楚。我们在结肠癌小鼠模型中使用mimotopes的工作揭示了这些问题的重要见解。我们提出，基于刺激自然反应的T细胞库来鉴定mimotopes将显著提高mimotope疫苗接种的效果。
Immune recognition and elimination of cancerous cells is the primary goal of cancer immunotherapy. However, obstacles including immune tolerance and tumor-induced immunosuppression often limit beneficial immune responses. Vaccination is one proposed intervention that may help to overcome these issues and is an active area of study in cancer immunotherapy. Immunizing with tumor antigenic peptides is a promising, straight-forward vaccine strategy hypothesized to boost preexisting antitumor immunity. However, tumor antigens are often weak T cell agonists, attributable to several mechanisms, including immune self-tolerance and poor immunogenicity of self-derived tumor peptides. One strategy for overcoming these mechanisms is vaccination with mimotopes, or peptide mimics of tumor antigens, which alter the antigen presentation and/or T cell activation to increase the expansion of tumor-specific T cells. Evaluation of mimotope vaccine strategies has revealed that even subtle alterations in peptide sequence can dramatically alter antigen presentation and T cell receptor recognition. Most of this research has been performed using T cell clones, which may not be accurate representations of the naturally occurring antitumor response. The relationship between clones generated after mimotope vaccination and the polyclonal T cell repertoire is unclear. Our work with mimotopes in a mouse model of colon carcinoma has revealed important insights into these issues. We propose that the identification of mimotopes based on stimulation of the naturally responding T cell repertoire will dramatically improve the efficacy of mimotope vaccination.
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影响因子：
32.4
作者：
Adams JJ;Narayanan S;Liu B;Birnbaum ME;Kruse AC;Bowerman NA;Chen W;Levin AM;Connolly JM;Zhu C;Kranz DM;Garcia KC
通讯作者：
Garcia KC
影响因子：
4.4
作者：
Chen, Ji-Li;Morgan, Anthony J.;Cerundolo, Vincenzo
通讯作者：
Cerundolo, Vincenzo
影响因子：
15.3
作者：
Colella, T A;Bullock, T N;Russell, L B;Mullins, D W;Overwijk, W W;Luckey, C J;Pierce, R A;Restifo, N P;Engelhard, V H
通讯作者：
Engelhard, V H
影响因子：
9
作者：
Coley, W B
通讯作者：
Coley, W B
影响因子：
4.4
作者：
Borbulevych, OY;Baxter, TK;Baker, BM
通讯作者：
Baker, BM