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乳腺癌中的肽疫苗:临床应答的免疫学基础。

Peptide vaccines in breast cancer: The immunological basis for clinical response.

机构信息

Laboratório de Osteoimunologia e Imunologia dos Tumores, Instituto de Ciências Biomédicas (ICBIM) - Universidade Federal de Uberlândia - UFU, Uberlândia, MG, Brazil.

Laboratório de Osteoimunologia e Imunologia dos Tumores, Instituto de Ciências Biomédicas (ICBIM) - Universidade Federal de Uberlândia - UFU, Uberlândia, MG, Brazil.

出版信息

Biotechnol Adv. 2015 Dec;33(8):1868-77. doi: 10.1016/j.biotechadv.2015.10.013. Epub 2015 Oct 30.

Abstract

This review discusses peptide-based vaccines in breast cancer, immune responses and clinical outcomes, which include studies on animal models and phase I, phase I/II, phase II and phase III clinical trials. Peptide-based vaccines are powerful neoadjuvant immunotherapies that can directly target proteins expressed in tumor cells, mainly tumor-associated antigens (TAAs). The most common breast cancer TAA epitopes are derived from MUC1, HER2/neu and CEA proteins. Peptides derived from TAAs could be successfully used to elicit CD8 and CD4 T cell-specific responses. Thus, choosing peptides that adapt to natural variations of human leukocyte antigen (HLA) genes is critical. The most attractive advantage is that the target response is more specific and less toxic than for other therapies and vaccines. Prominent studies on NeuVax - E75 (epitope for HER2/neu and GM-CSF) in breast cancer and DPX-0907 (HLA-A2-TAAs) expressed in breast cancer, ovarian and prostate cancer have shown the efficacy of peptide-based vaccines as neoadjuvant immunotherapy against cancer. Future peptide vaccine strategies, although a challenge to be applied in a broad range of breast cancers, point to the development of degenerate multi-epitope immunogens against multiple targets.

摘要

本文综述了乳腺癌中基于肽的疫苗、免疫反应和临床结局,其中包括动物模型以及 I 期、I/II 期、II 期和 III 期临床试验的研究。基于肽的疫苗是强大的新辅助免疫疗法,可以直接针对肿瘤细胞中表达的蛋白质,主要是肿瘤相关抗原(TAA)。最常见的乳腺癌 TAA 表位来源于 MUC1、HER2/neu 和 CEA 蛋白。源自 TAA 的肽可成功引发 CD8 和 CD4 T 细胞特异性反应。因此,选择适应人类白细胞抗原(HLA)基因自然变异的肽至关重要。最具吸引力的优势是,与其他疗法和疫苗相比,针对目标的反应更具特异性且毒性更小。在乳腺癌中针对 NeuVax-E75(HER2/neu 和 GM-CSF 的表位)和 DPX-0907(在乳腺癌、卵巢癌和前列腺癌中表达的 HLA-A2-TAA)的突出研究表明,基于肽的疫苗作为癌症的新辅助免疫疗法具有疗效。未来的肽疫苗策略虽然在广泛的乳腺癌中应用具有挑战性,但指向针对多个靶标的退化多表位免疫原的开发。

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