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Discovery of a self-assembling and self-adjuvant lipopeptide as a saccharide-free peptide vaccine targeting EGFRvIII positive cutaneous melanoma†
Biomaterials Science ( IF 5.8 ) Pub Date : 2018-03-01 00:00:00 , DOI: 10.1039/c8bm00017d
Yujuan Chen 1, 2, 3, 4, 5 , Fengjiao Yuan 1, 2, 3, 4, 5 , Xian Jiang 1, 2, 3, 4, 5 , Qing Lv 1, 2, 3, 4, 5 , Na Luo 6, 7, 8, 9 , Changyang Gong 1, 2, 3, 4, 5 , Chunting Wang 1, 2, 3, 4, 5 , Li Yang 1, 2, 3, 4, 5 , Gu He 1, 2, 3, 4, 5
Affiliation  

Recently, tumor immunotherapy has achieved great progress in the treatment of hematological and solid neoplasms. The DC vaccines, KLH-conjugated vaccines or glycosylated peptide vaccines can efficiently induce immune responses against tumors. In the current study, we have discovered cholesteryl PADRE-EGFRvIII epitope-conjugated lipopeptide self-assembled micelles as a potential self-adjuvant vaccine against cutaneous melanoma. The lipopeptide vaccines were synthesized using a standard solid phase peptide synthesis method, and these vaccines could elicit both a humoral and a cellular immune response to EGFRvIII positive melanoma cells. Their high humoral immunoreaction stimulation properties in combination with their cytotoxic T-cell eliciting properties provide them with potent tumor inhibitory capacity. In therapeutic and preventive xenograft models of B16-EGFRvIII melanoma cells, the self-adjuvant lipopeptide vaccine micelles efficiently prevented tumor growth as well as tumorigenesis. Our results provide a novel platform for eliciting immune responses to non-antigenic cancer-related epitopes in peptide cancer vaccine discovery and development.

中文翻译:

发现了一种自组装和自佐剂脂肽作为针对EGFRvIII阳性皮肤黑素瘤的无糖肽疫苗

近来,肿瘤免疫疗法在血液学和实体瘤的治疗中取得了很大的进展。DC疫苗,KLH缀合疫苗或糖基化肽疫苗可以有效地诱导针对肿瘤的免疫应答。在当前的研究中,我们发现胆固醇基PADRE-EGFRvIII表位缀合的脂肽自组装胶束可作为对抗皮肤黑素瘤的潜在自佐剂疫苗。使用标准的固相肽合成方法合成脂肽疫苗,这些疫苗可引起针对EGFRvIII阳性黑色素瘤细胞的体液和细胞免疫应答。它们的高体液免疫反应刺激特性与细胞毒性T细胞诱导特性相结合,为他们提供了强大的肿瘤抑制能力。在B16-EGFRvIII黑色素瘤细胞的治疗性和预防性异种移植模型中,脂蛋白自佐剂疫苗胶束有效地防止了肿瘤的生长以及肿瘤的发生。我们的结果为在肽癌疫苗发现和开发中引发针对非抗原性癌症相关表位的免疫应答提供了一个新颖的平台。
更新日期:2018-03-01
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