The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide.
The enhanced antitumor-specific immune response with mannose- and CpG-ODN-coated liposomes delivering TRP2 peptide.
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作者：
Lai C;Duan S;Ye F;Hou X;Li X;Zhao J;Yu X;Hu Z;Tang Z;Mo F;Yang X;Lu X
目的：树突状细胞（DC）为基础的肿瘤疫苗是一种新兴的、有效的免疫治疗形式。至于任何新技术，仍然有相当大的挑战需要解决。在这里，我们研究了一种新的脂质体疫苗，M/CpG-ODN-TRP 2-Lipo的抗肿瘤潜力。研究方法：我们将靶向DC的甘露糖和免疫佐剂CpG-ODN组装在脂质体表面，并负载黑色素瘤特异性多肽TRP 2180 -188作为脂质体疫苗。用M/CpG-ODN-TRP 2-Lipo诱导DCs的活化和体内抗肿瘤特异性免疫应答。结果：脂质体颗粒在体外可被DC有效摄取。这种摄取导致DC的活化增强，如通过MHC II、CD 80和CD 86的上调所测量的。M/CpG-ODN-TRP 2-Lipo能有效抑制B16黑色素瘤的生长，延长小鼠的生存期。这种疗法显著减少了髓源性抑制细胞（MDSC）和调节性T细胞的数量，同时增加了活化T细胞、肿瘤抗原特异性CD 8+细胞毒性T细胞和产生干扰素-γ的细胞的数量。同时，发现它抑制肿瘤血管生成和肿瘤细胞增殖，以及上调它们的凋亡。有趣的是，在给予M/CpG-ODN-TRP 2-Lipo后，MyD 88敲除小鼠的中位存活时间显著短于野生型小鼠。结论：该疫苗的抗肿瘤活性部分依赖于Myd 88信号通路。有趣的是，与基于全肿瘤细胞裂解物的疫苗相比，基于肿瘤特异性抗原肽的疫苗M/CpG-ODN-TRP 2-Lipo提高了荷瘤小鼠的存活率，并增强了其抗肿瘤应答。总之，我们描述了一种新的疫苗制剂，M/CpG-ODN-TRP 2-Lipo，其目的是通过减轻肿瘤中的免疫抑制环境来改善抗肿瘤反应。
Purpose: Dendritic cell (DC)-based cancer vaccines is a newly emerging and potent form of immune therapy. As for any new technology, there are still considerable challenges that need to be addressed. Here, we investigate the antitumor potential of a novel liposomal vaccine, M/CpG-ODN-TRP2-Lipo. Methods: We developed a vaccination strategy by assembling the DC-targeting mannose and immune adjuvant CpG-ODN on the surface of liposomes, which were loaded with melanoma-specific TRP2180-188 peptide as liposomal vaccine. M/CpG-ODN-TRP2-Lipo treatment was used to intendedly induce activation of DCs and antitumor- specific immune response in vivo. Results: Our results demonstrated in vitro that the prepared liposomal particles were efficiently taken up by DCs. This uptake led to an enhanced activation of DCs, as measured by the upregulation of MHC II, CD80, and CD86. Furthermore, M/CpG-ODN-TRP2-Lipo effectively inhibited the growth of implanted B16 melanoma and prolonged the survival of mice. This therapy significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, while simultaneously increasing the number of activated T cells, tumor antigen-specific CD8+ cytotoxic T cells, and interferon-γ-producing cells. At the same time, it was found to suppress tumor angiogenesis and tumor cell proliferation, as well as up-regulate their apoptosis. Interestingly, MyD88-knockout mice had significantly shorter median survival times compared to wild-type mice following the administration of M/CpG-ODN-TRP2-Lipo. Conclusions: The results suggested that the antitumor activities of the vaccine partially rely on the Myd88 signaling pathway. Interestingly, compared to whole tumor cell lysate-based vaccine, M/CpG-ODN-TRP2-Lipo, tumor specific antigen peptide-based vaccine, improved survival of tumor-bearing mice as well as enhanced their antitumor responses. All in all, we describe a novel vaccine formulation, M/CpG-ODN-TRP2-Lipo, with the aim of improving antitumor responses by alleviating the immunosuppressive environment in tumors.