Efficacy of MAGE-A4 long peptide as a universal immunoprevention cancer vaccine.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-07-03 DOI:10.1186/s12935-024-03421-2

Lanqi Cen, Zhe Zhang, Yi Sun, Nandie Wu, Jie Shao, Zhaoye Qian, Manman Tian, Yaohua Ke, Baorui Liu

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Abstract

Background: The clinical application of peptide vaccines in tumor immunotherapy holds significant promise. Peptide-based tumor vaccines are currently subject to certain limitations in clinical trials, including the challenge of inducing a sustained response from CD4⁺ T helper cells and cytotoxic T lymphocytes (CTL), as well as human leukocyte antigen (HLA) restrictions.

Methods: Through the utilization of biological information methodology, a screening process was conducted to identify three potential long peptides that are specifically targeted by the MAGE-A4 antigen. The candidate long peptides were subjected to in vitro testing using human peripheral blood lymphocytes as samples to evaluate their immunogenicity and immune function. The antitumor properties and preliminary mechanism of the long peptide vaccine were investigated through the use of a mouse model designed for the prevention of triple negative breast cancer (TNBC).

Results: Three predicted multi-epitope long peptides targeting MAGE-A4 have shown to have a strong immunogenicity, with a total positive rate of 72% across different HLA subtypes in Chinese populations. they can also increase the levels of the costimulatory factor CD137 and tumor necrosis factor-alpha (TNF-α), activate T cells, and boost the cytotoxic activity. Results from an animal study have revealed that the long-peptide vaccine, both on its own and in combination with R848, has displayed impressive anti-tumor and target-specific capabilities. Moreover, it has the ability to increase the expression of effector memory T cells and central memory T cells.

Conclusions: This study was the first to screen three multi-epitope long peptides targeting MAGE-A4 and assess their immunogenicity, immune function, and potential as adjuvant peptides. The results showed that the MAGE-A4 long peptide vaccine can be used as a novel immunoprophylaxis method to prevent TNBC. Moreover, the proposed development model is capable of screening multiple target antigens, which lead to its clinical application.

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MAGE-A4 长肽作为通用免疫预防癌症疫苗的功效。

背景：多肽疫苗在肿瘤免疫疗法中的临床应用前景广阔。基于多肽的肿瘤疫苗目前在临床试验中受到某些限制，包括诱导 CD4+ T 辅助细胞和细胞毒性 T 淋巴细胞（CTL）产生持续反应的挑战，以及人类白细胞抗原（HLA）的限制：方法：通过利用生物信息学方法，筛选出三种潜在的长肽，它们是 MAGE-A4 抗原的特异性靶标。以人类外周血淋巴细胞为样本，对候选长肽进行体外测试，评估其免疫原性和免疫功能。通过使用为预防三阴性乳腺癌（TNBC）而设计的小鼠模型，研究了长肽疫苗的抗肿瘤特性和初步机制：结果：三种预测的以MAGE-A4为靶点的多表位长肽具有很强的免疫原性，在中国不同HLA亚型人群中的总阳性率为72%，它们还能提高成本刺激因子CD137和肿瘤坏死因子-α（TNF-α）的水平，激活T细胞，增强细胞毒活性。一项动物实验结果表明，无论是单独使用还是与 R848 联用，长肽疫苗都表现出了惊人的抗肿瘤能力和靶向特异性。此外，它还能增加效应记忆 T 细胞和中枢记忆 T 细胞的表达：本研究首次筛选了三种靶向MAGE-A4的多表位长肽，并评估了它们的免疫原性、免疫功能和作为佐剂肽的潜力。结果表明，MAGE-A4 长肽疫苗可用作预防 TNBC 的新型免疫预防方法。此外，所提出的开发模型能够筛选多种目标抗原，从而促进其临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.