癌症疫苗可以与检查点抑制剂联合使用，以最佳地刺激抗肿瘤免疫反应。抗原呈递细胞 (APC) 摄取疫苗抗原是 T 细胞启动的先决条件，但通常依赖于非特异性机制。在这里，我们开发了一种新型疫苗接种策略，该策略由含有癌症抗原的脂质体与 CD169 或 DC-SIGN 特异性纳米抗体（单域抗体）缀合组成，以实现 APC 的特异性摄取。我们的研究表明，与对照脂质体或具有 CD169 和 DC-SIGN 天然配体的脂质体相比，人和鼠 CD169 和 DC-SIGN APC 在体外和体内均能有效摄取纳米抗体脂质体。 CD169 纳米抗体脂质体的摄取导致人类 APC 的 T 细胞活化增加，并刺激小鼠模型中的初始 T 细胞启动。总之，虽然纳米体脂质体之前已被用来将药物引导至肿瘤，但在这里我们表明，纳米体脂质体可以用作疫苗接种策略，可以扩展到 APC 上的其他受体，以引发针对肿瘤抗原的有效免疫反应。 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

Cancer vaccines can be utilized in combination with checkpoint inhibitors to optimally stimulate the anti-tumor immune response. Uptake of vaccine antigen by antigen presenting cells (APCs) is a prerequisite for T cell priming, but often relies on non-specific mechanisms. Here, we have developed a novel vaccination strategy consisting of cancer antigen-containing liposomes conjugated with CD169- or DC-SIGN-specific nanobodies (single domain antibodies) to achieve specific uptake by APCs. Our studies demonstrate efficient nanobody liposome uptake by human and murine CD169+ and DC-SIGN+ APCs in vitro and in vivo when compared to control liposomes or liposomes with natural ligands for CD169 and DC-SIGN. Uptake of CD169 nanobody liposomes resulted in increased T cell activation by human APCs and stimulated naive T cell priming in mouse models. In conclusion, while nanobody liposomes have previously been utilized to direct drugs to tumors, here we show that nanobody liposomes can be applied as vaccination strategy that can be extended to other receptors on APCs in order to elicit a potent immune response against tumor antigens.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.