Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, QC, Canada.
Department of Biomedical Sciences, Université de Montréal, Montréal, QC, Canada.
Cell Rep Med. 2022 Feb 25;3(3):100534. doi: 10.1016/j.xcrm.2022.100534. eCollection 2022 Mar 15.
The cross-presenting capacity of dendritic cells (DCs) can be limited by non-specific degradation during endosome maturation. To bypass this limitation, we present in this study a new Accum-based formulation designed to promote endosome-to-cytosol escape. Treatment of primary DCs with Accum linked to the xenoantigen ovalbumin (OVA) triggers endosomal damages and enhances protein processing. Despite multiple challenges using ascending doses of tumor cells, DC prophylactic vaccination results in complete protection due to increased levels of effector CD4 and CD8 T cells as well as high production of pro-inflammatory mediators. When combined with anti-PD-1, therapeutic vaccination using both syngeneic and allogeneic Accum-OVA-pulsed DCs triggers potent anti-tumoral responses. The net outcome culminates in increased CD11c, CD8, and NK infiltration along with a high CD8/Treg ratio. These highly favorable therapeutic effects highlight the promising potential of Accum as a distinct and potent technology platform suitable for the design of next generation cell cancer vaccines.
树突状细胞（DC）的交叉呈递能力可在内涵体成熟过程中受到非特异性降解的限制。为了克服这一限制，我们在本研究中提出了一种新的 Accum 制剂，旨在促进内涵体向细胞质逃逸。用与异源抗原卵清蛋白（OVA）偶联的 Accum 处理原代 DC 会引发内涵体损伤并增强蛋白加工。尽管使用递增剂量的肿瘤细胞面临多重挑战，但由于效应性 CD4 和 CD8 T 细胞水平升高以及促炎介质的大量产生，DC 预防性疫苗接种可实现完全保护。当与抗 PD-1 联合使用时，用同种和同种异体 Accum-OVA 脉冲处理的 DC 进行的治疗性疫苗接种可引发强烈的抗肿瘤反应。最终结果表现为 CD11c、CD8 和 NK 浸润增加，同时 CD8/Treg 比值升高。这些非常有利的治疗效果突显了 Accum 作为一种独特而有效的技术平台的巨大潜力，非常适合设计下一代细胞癌症疫苗。
