Synthetic tumor-specific antigenic peptides with a strong affinity to HLA-A2 elicit anti-breast cancer immune response through activating CD8+ T cells.,European Journal of Medicinal Chemistry

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Synthetic tumor-specific antigenic peptides with a strong affinity to HLA-A2 elicit anti-breast cancer immune response through activating CD8+ T cells.
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-01-11 , DOI: 10.1016/j.ejmech.2020.112051
Wei Shi ₁ , Qianqian Qiu ₂ , Zhenzhen Tong ₁ , Weiwei Guo ₁ , Feng Zou ₁ , Ziying Feng ₁ , Yao Wang ₃ , Wenlong Huang ₄ , Hai Qian ₄

Affiliation

Researches on tumor-associated antigen have become a hot target in immunotherapy, but it stagnated in the pre-clinical/clinical stages. Here, we developed a series of MAGE-A1-restricted antigenic peptides, which exhibited prominent inhibiting effect on specific breast cancer. Peptides were synthesized by Fmoc solid phase method and analyzed by online servers. The stability and affinity to HLA-A2 was assessed by inverted fluorescence and flow cytometry qualitatively and quantitatively. In vitro effect on dendritic cells (DCs) maturation was observed by morphology and surface markers. The secretion of IFN-γ in the supernatant was detected by co-incubation of DCs loaded with as-synthesized peptides and CD8+ T lymphocytes. The specific immune response was evaluated against 4 cell lines, and the response in MCF-7 xenografted BALB/c nude mice were further assessed. Most of the derived peptides, especially I-6, showed great HLA-A2 binding ability. Compared with cytokines, I-6 significantly induced DCs maturation and promoted CD8+ T lymphocytes activation. Additionally, it is more specific for the lethality of MAGE & HLA-A2 double positive cells compared with others. We successfully developed I-6 with a high affinity to HLA-A2 which could induce strong specific immune response. It could be a potential candidate for breast cancer immunotherapy, which deserves further studies.

中文翻译：

对HLA-A2具有强亲和力的合成肿瘤特异性抗原肽通过激活CD8 + T细胞引发抗乳腺癌免疫反应。

肿瘤相关抗原的研究已成为免疫治疗的热点，但在临床前/临床阶段却停滞不前。在这里，我们开发了一系列的MAGE-A1限制性抗原肽，对特定的乳腺癌表现出显着的抑制作用。通过Fmoc固相法合成肽，并通过在线服务器进行分析。通过倒置荧光和流式细胞术定性和定量地评估对HLA-A2的稳定性和亲和力。通过形态学和表面标记观察到体外对树突状细胞（DCs）成熟的影响。通过将含有合成肽和CD8 + T淋巴细胞的DC共孵育，检测上清液中IFN-γ的分泌。针对4种细胞系评估了特异性免疫反应，并进一步评估了MCF-7异种移植BALB / c裸鼠的反应。大多数衍生的肽，特别是I-6，显示出强大的HLA-A2结合能力。与细胞因子相比，I-6显着诱导DC成熟并促进CD8 + T淋巴细胞活化。此外，与其他相比，它对MAGE和HLA-A2双阳性细胞的致死性更具特异性。我们成功开发了对HLA-A2具有高亲和力的I-6，可以诱导强烈的特异性免疫反应。它可能是乳腺癌免疫治疗的潜在候选者，值得进一步研究。与其他相比，它对MAGE和HLA-A2双阳性细胞的致死性更具特异性。我们成功开发了对HLA-A2具有高亲和力的I-6，可以诱导强烈的特异性免疫反应。它可能是乳腺癌免疫治疗的潜在候选者，值得进一步研究。与其他相比，它对MAGE和HLA-A2双阳性细胞的致死性更具特异性。我们成功开发了对HLA-A2具有高亲和力的I-6，可以诱导强烈的特异性免疫反应。它可能是乳腺癌免疫治疗的潜在候选者，值得进一步研究。

更新日期：2020-01-13

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