A major challenge for the development of anticancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant‐free manner. In this respect, we present a simple strategy to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)‐restricted peptide epitope (called E. nanofibers) without the use of adjuvant. We demonstrate that incorporation of Tat, a cell‐penetrating peptide (CPP) of the HIV transactivator protein, into E. nanofibers remarkably enhanced tumor‐specific CD8+ T cell responses. E. nanofibers containing 12.5% Tat peptide (E.Tat_12.5 nanofiber) increased antigen cross‐presentation by bone marrow‐derived dendritic cells as compared with E. nanofibers, or E. nanofibers containing 25 or 50% the Tat peptide. Uptake of KFE8.Tat_12.5 nanofibers by dendritic cells (DCs) was significantly increased compared with KFE8 nanofiber lacking Tat. Peritoneal and lymph node DCs of mice immunized with E.Tat_12.5 nanofibers exhibited increased presentation of the H2kb‐epitope (reminiscent for cross‐presentation) compared with DCs obtained from E. nanofiber vaccinated mice. Tetrameric and intracellular cytokine staining revealed that vaccination with E.Tat_12.5 triggered a robust and specific CD8+ T lymphocyte response, which was more pronounced than in mice vaccinated with E. nanofibers alone. Furthermore, E.Tat_12.5 nanofibers were more potent than E. nanofiber to induce antitumor immune response and tumor‐infiltrating IFN‐γ CD8 T lymphocyte. In terms of cancer vaccine development, we propose that harnessing the nanofiber‐based vaccine platform with incorporated Tat peptide could present a simple and promising strategy to induce highly effective antitumor immune response.

中文翻译：

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将 Tat 细胞穿透肽掺入纳米纤维可改善各自的抗肿瘤免疫反应。

开发抗癌疫苗的一个主要挑战是以无佐剂的方式诱导安全有效的免疫反应，特别是由 CD8+T 淋巴细胞介导的免疫反应。在这方面，我们提出了一种简单的策略，使用带有 I 类 (Kb) 限制性肽表位（称为 E. 纳米纤维）的 KFE8 纳米纤维来改善特定的 CD8+ T 细胞反应，而无需使用佐剂。我们证明，将 HIV 反式激活蛋白的细胞穿透肽 (CPP) 掺入大肠杆菌纳米纤维中可显着增强肿瘤特异性 CD8+ T 细胞反应。E. 含有 12.5% Tat 肽的纳米纤维 (E.Tat _12.5纳米纤维）与 E. 纳米纤维或含有 25% 或 50% Tat 肽的 E. 纳米纤维相比，增加了骨髓来源的树突细胞的抗原交叉呈递。与缺乏 Tat 的 KFE8 纳米纤维相比，树突状细胞 (DC)对 KFE8.Tat _12.5纳米纤维的吸收显着增加。与从接种 E.Tat _12.5纳米纤维的小鼠中获得的 DC 相比，用 E.Tat _12.5纳米纤维免疫的小鼠的腹膜和淋巴结 DC表现出更多的 H2kb 表位呈递（让人联想到交叉呈递）。四聚体和细胞内细胞因子染色显示接种 E.Tat _12.5引发了强烈且特异性的 CD8+ T 淋巴细胞反应，这比单独接种 E. 纳米纤维的小鼠更为明显。此外，E.Tat _12.5纳米纤维在诱导抗肿瘤免疫反应和肿瘤浸润性 IFN-γ CD8 T 淋巴细胞方面比 E. 纳米纤维更有效。在癌症疫苗开发方面，我们提出利用基于纳米纤维的疫苗平台与掺入的 Tat 肽可以提供一种简单而有前景的策略来诱导高效的抗肿瘤免疫反应。