摘要
目的:基于T细胞应答的免疫治疗是一种很有前途的肿瘤治疗方法.本研究旨在重新设计基于人工表位的免疫原,dna疫苗候选。评价ST黑色素瘤对体外产生的T细胞的细胞毒性作用. 方法:采用原计算方法预测T细胞表位,设计多表位黑色素瘤抗原。将编码靶抗原的人工基因克隆到dna va中。CCIN质粒载体转染DNA疫苗的HEK-293 T细胞在转录水平和翻译水平上均证实了靶基因的表达。树突状细胞HLA-A*02:01供者M粘附外周血单个核细胞。自体抗原提呈树突状细胞共培养诱导效应淋巴细胞对MEL的杀伤活性用乳酸脱氢酶释放法检测瘤Mel is细胞。用细胞内细胞因子染色和流式细胞术检测颗粒酶B产生CD8 T细胞的比例。 结果:构建了两种DNA疫苗pmel-tci和pmel-A 0201-编码6种免疫显性黑色素瘤抗原T细胞表位的多肽(NY-ESO-1,MART 1,MAGE-A1,MAG)。电子-A11,法师-A3,和法师-C1)。转染DNA疫苗构建的树突状细胞既能刺激自体淋巴细胞介导的肿瘤细胞毒性,也能刺激CD介导的颗粒酶B的产生。8个T细胞,PMEL-A 0201是最有效的。 结论:该方法可作为肿瘤免疫治疗疫苗设计的通用平台。
关键词: 黑色素瘤,抗肿瘤DNA疫苗,T细胞表位,人工多表位抗原,细胞毒性反应,MAGE。
Current Gene Therapy
Title:Design of Artificial Immunogens Containing Melanoma-associated T-cell Epitopes
Volume: 18 Issue: 6
关键词: 黑色素瘤,抗肿瘤DNA疫苗,T细胞表位,人工多表位抗原,细胞毒性反应,MAGE。
摘要: Objective: Immunotherapy based on induction of T-cell responses is a promising approach to cancer treatment. The study aims to design artificial epitope-based immunogens, DNA vaccine candidates against melanoma and evaluate their ability to stimulate tumor cytotoxicity of ex vivo generated T-cells.
Methods: The original computational methods were used for predicting T-cell epitopes and designing polyepitope melanoma antigens. Artificial genes encoding the target antigens were cloned into DNA vaccine plasmid vector. Target gene expression was confirmed both at transcriptional and translational level in HEK-293T cells transfected with DNA-vaccine constructs. Dendritic cells were generated from adherent peripheral blood mononuclear cells of HLA-A*02:01+ donors. Cytotoxic activity of effector lymphocytes stimulated in co-culture with autologous antigen-presenting dendritic cells towards melanoma Mel Is cells was assessed with lactate dehydrogenase release assay. The proportion of granzyme B producing CD8+ T-cells was estimated using intracellular cytokine staining and flow cytometry.
Results: Two DNA vaccine constructions were created - pMEL-TCI and pMEL-A0201 - encoding polypeptides containing T-cell epitopes of six immunodominant melanoma antigens (NY-ESO-1, MART1, MAGE-A1, MAGE-A11, MAGE-A3, and MAGE-C1). Dendritic cells transfected with DNA vaccine constructs were found to stimulate both tumor cytotoxicity mediated by autologous lymphocytes and granzyme B production by CD8+ T-cells, and pMEL-A0201 was found to be the most efficient.
Conclusion: The described approach may become a common platform for designing immunotherapeutic vaccines against oncological diseases.
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Cite this article as:
Design of Artificial Immunogens Containing Melanoma-associated T-cell Epitopes, Current Gene Therapy 2018; 18 (6) . https://dx.doi.org/10.2174/1566523218666181113112829
DOI https://dx.doi.org/10.2174/1566523218666181113112829 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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