Division of Immunology and Allergy, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, SE-171 64 Stockholm, Sweden; and.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
J Immunol. 2019 Aug 15;203(4):825-834. doi: 10.4049/jimmunol.1801628. Epub 2019 Jul 10.
Extracellular vesicles (EV) are candidates for cancer immunotherapy because of their capacity to stimulate tumor-specific activity in vivo. However, clinical trials using peptide-loaded autologous EVs have so far only showed moderate T cell responses, suggesting a need for optimization of EV-induced immunity in humans. We previously demonstrated that induction of Ag-specific CD8 T cells and antitumor responses to whole Ag were independent of MHC class I on EVs and hypothesized that multiple injections of allogeneic EVs could potentiate Ag-specific responses. In this study, we show that the allogeneic EV from mouse bone marrow-derived dendritic cells enhances Ag-specific CD8 T cell, follicular helper T cell, and Ag-specific Ab responses. EV-injected mice demonstrated Ag-specific memory after 4 mo, with the highest Ab avidity in mice receiving double allogeneic EV injections. Reduced B16mOVA melanoma tumor growth was shown in all EV-injected groups. Our findings support the application of allogeneic EVs for therapeutic use in clinical studies in which an adaptive immune response is desired.
细胞外囊泡（EV）是癌症免疫治疗的候选物，因为它们能够在体内刺激肿瘤特异性活性。然而，迄今为止，使用负载肽的自体 EV 进行的临床试验仅显示出中等强度的 T 细胞反应，这表明需要优化人类 EV 诱导的免疫。我们之前证明，Ag 特异性 CD8 T 细胞的诱导和对整个 Ag 的抗肿瘤反应与 EV 上的 MHC 类 I 无关，并假设多次注射同种异体 EV 可以增强 Ag 特异性反应。在这项研究中，我们表明，来自小鼠骨髓来源树突状细胞的同种异体 EV 增强了 Ag 特异性 CD8 T 细胞、滤泡辅助 T 细胞和 Ag 特异性 Ab 反应。接受 EV 注射的小鼠在 4 个月后表现出 Ag 特异性记忆，在接受两次同种异体 EV 注射的小鼠中具有最高的 Ab 亲和力。在所有接受 EV 注射的组中，B16mOVA 黑色素瘤肿瘤生长均减少。我们的研究结果支持同种异体 EV 在临床研究中的应用，在这些研究中需要适应性免疫反应。
