Watanabe Akihiro, Yamashita Kimihiro, Fujita Mitsugu, Arimoto Akira, Nishi Masayasu, Takamura Shiki, Saito Masafumi, Yamada Kota, Agawa Kyosuke, Mukoyama Tomosuke, Ando Masayuki, Kanaji Shingo, Matsuda Takeru, Oshikiri Taro, Kakeji Yoshihiro
Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
Center for Medical Education and Clinical Training, Kindai University Faculty of Medicine, 377-2 Onohigashi, Osaka 589-0014, Japan.
Cancers (Basel). 2021 Dec 30;14(1):171. doi: 10.3390/cancers14010171.
(1) Background: Cancer vaccines are administered to induce cytotoxic CD8 T cells (CTLs) specific for tumor antigens. Invariant natural killer T (iNKT) cells, the specific T cells activated by α-galactosylceramide (α-GalCer), play important roles in this process as they are involved in both innate and adaptive immunity. We developed a new cancer vaccine strategy in which dendritic cells (DCs) were loaded with an exogenous ovalbumin (OVA) protein by electroporation (EP) and pulsed with α-GalCer. (2) Methods: We generated bone marrow-derived DCs from C57BL/6 mice, loaded full-length ovalbumin proteins to the DCs by EP, and pulsed them with α-GalCer (OVA-EP-galDCs). The OVA-EP-galDCs were intravenously administered to C57BL/6 mice as a vaccine. We then investigated subsequent immune responses, such as the induction of iNKT cells, NK cells, intrinsic DCs, and OVA-specific CD8 T cells, including tissue-resident memory T (T) cells. (3) Results: The OVA-EP-galDC vaccine efficiently rejected subcutaneous tumors in a manner primarily dependent on CD8 T cells. In addition to the OVA-specific CD8 T cells both in early and late phases, we observed the induction of antigen-specific T cells in the skin. (4) Conclusions: The OVA-EP-galDC vaccine efficiently induced antigen-specific antitumor immunity, which was sustained over time, as shown by the T cells.
(1) 背景:癌症疫苗用于诱导针对肿瘤抗原的细胞毒性CD8 T细胞(CTL)。不变自然杀伤T(iNKT)细胞是由α-半乳糖神经酰胺(α-GalCer)激活的特异性T细胞,由于它们参与固有免疫和适应性免疫,在这一过程中发挥重要作用。我们开发了一种新的癌症疫苗策略,即通过电穿孔(EP)将外源性卵清蛋白(OVA)蛋白负载到树突状细胞(DC)中,并用α-GalCer进行脉冲处理。(2) 方法:我们从C57BL/6小鼠中生成骨髓来源的DC,通过EP将全长卵清蛋白蛋白负载到DC中,并用α-GalCer进行脉冲处理(OVA-EP-galDC)。将OVA-EP-galDC作为疫苗静脉注射给C57BL/6小鼠。然后我们研究了随后的免疫反应,如iNKT细胞、NK细胞、固有DC和OVA特异性CD8 T细胞的诱导,包括组织驻留记忆T(T)细胞。(3) 结果:OVA-EP-galDC疫苗主要依赖CD8 T细胞有效地排斥皮下肿瘤。除了早期和晚期的OVA特异性CD8 T细胞外,我们还观察到皮肤中抗原特异性T细胞的诱导。(4) 结论:如T细胞所示,OVA-EP-galDC疫苗有效地诱导了抗原特异性抗肿瘤免疫,且这种免疫随时间持续存在。