Sher Yuh-Pyng, Chai Kit Man, Chen Wen-Ching, Shen Kuan-Yin, Chen I-Hua, Lee Ming-Hui, Chiu Fang-Feng, Liu Shih-Jen
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan.
Vaccines (Basel). 2020 Oct 21;8(4):620. doi: 10.3390/vaccines8040620.
Peptide vaccines are safe, and aim to elicit and expand tumor-specific immunity so as to eradicate tumors. However, achieving strong and long-lasting anti-tumor immunity with peptide vaccines for the antigen-specific treatment of cancer is challenging, in part because their efficacy depends on strong adjuvants or immunomodulators. We approached this problem by conjugating an epitope-based cancer vaccine with a lipidated sequence (an immunomodulator) to elicit a strong immune response. Lipidated and non-lipidated polyepitope proteins were generated that contained the universal T helper cell epitope (pan-DR), B cell epitopes, and the extended loop sequence of extracellular domain 2 of tumor-associated antigen L6 (TAL6). We show that the lipidated polyepitope cancer vaccine can activate bone marrow-derived dendritic cells, and trigger effective antigen-specific antibody and T helper cell responses, more effectively than the non-lipidated vaccine. Moreover, potent T cell immune responses were elicited in mice inoculated with the lipidated polyepitope cancer vaccine, providing protective antitumor immunity in mice bearing TAL6 tumors. Our study demonstrates that a lipidated polyepitope cancer vaccine could be employed to generate potent anti-tumor immune responses, including humoral and cellular immunity, which could be beneficial in the treatment of TAL6 cancer.
肽疫苗是安全的，旨在引发和扩大肿瘤特异性免疫以根除肿瘤。然而，使用肽疫苗进行癌症的抗原特异性治疗以实现强大且持久的抗肿瘤免疫具有挑战性，部分原因是其疗效取决于强效佐剂或免疫调节剂。我们通过将基于表位的癌症疫苗与脂化序列（一种免疫调节剂）偶联以引发强烈的免疫反应来解决这个问题。生成了脂化和非脂化的多表位蛋白，其包含通用T辅助细胞表位（泛DR）、B细胞表位以及肿瘤相关抗原L6（TAL6）细胞外结构域2的延伸环序列。我们表明，脂化的多表位癌症疫苗比非脂化疫苗更有效地激活骨髓来源的树突状细胞，并触发有效的抗原特异性抗体和T辅助细胞反应。此外，接种脂化多表位癌症疫苗的小鼠引发了强大的T细胞免疫反应，为携带TAL6肿瘤的小鼠提供了保护性抗肿瘤免疫。我们的研究表明，脂化的多表位癌症疫苗可用于产生强大的抗肿瘤免疫反应，包括体液免疫和细胞免疫，这可能对TAL6癌症的治疗有益。
