DNA疫苗因其高效的制造工艺而具有前景，但其免疫原性有限，因为它们不能有效诱导CD8 T细胞反应。一种有前途的方法是通过将抗原靶向树突状细胞来诱导交叉呈递。 Flt3L可以扩展1型常规DC的数量，从而改善交叉呈现。在本研究中，我们首先构建了表达可溶性PD1的DNA疫苗，发现仅用sPD1疫苗靶向DC的治疗效果有限。当该疫苗与Flt3L联合使用时，抗肿瘤效果显着增强。考虑到肿瘤的复杂性，单一方法可能无法激活大量有效的CD8 T细胞，我们根据不同肿瘤的特点，将不同的药物和疫苗与Flt3L进行组合。在4T1模型中，我们通过环磷酰胺减少Tregs。在Panc02模型中，我们使用aCD40增加了活化的DC。这两种策略均引发了强烈的 CD8 T 细胞反应并显着提高了治疗效果。我们的研究为 DC 靶向 DNA 疫苗与 Flt3L 结合的临床探索提供了重要支持。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。

DNA vaccines are prospective for their efficient manufacturing process, but their immunogenicity is limited as they cannot efficiently induce CD8+ T cell responses. A promising approach is to induce cross-presentation by targeting antigens to DCs. Flt3L can expand the number of type 1 conventional DCs and thereby improve cross-presentation. In this study, we first constructed a DNA vaccine expressing soluble PD1 and found that the therapeutic effect of targeting DCs with only the sPD1 vaccine was limited. When combined the vaccine with Flt3L, the anti-tumor effect was significantly enhanced. Considering the complexity of tumors and that a single method may not be able to activate a large number of effective CD8+ T cells, we combined different drugs and the vaccine with Flt3L based on the characteristics of different tumors. In 4T1 model, we reduced Tregs through cyclophosphamide. In Panc02 model, we increased activated DCs by using aCD40. Both strategies triggered strong CD8+ T cell responses and significantly improved the therapeutic effect. Our study provides important support for the clinical exploration of DC-targeted DNA vaccines in combination with Flt3L.Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.