Abstract The advantage of rapid tumor growth over slow immune induction often limits the efficiency of cancer therapeutic vaccines. Many functionalized micro-/nano-vaccines are shown to enhance cancer immunotherapy, but few studies correlate the therapeutic efficacy of these micro-/nano-vaccines to the vaccination route such as intravenous (IV), subcutaneous (SC) injection or their combination. Herein, we employed classical “priming + boosting” vaccination strategy to investigate the influence of four vaccination combinations (IV + IV, IV + SC, SC + IV and SC + SC) of nanovaccines on the anti-tumor therapeutic efficacy in mice bearing E.G7-OVA-lymphoma and B16F10-melanoma. The nanovaccines were constructed by loading antigen and CpG onto layered double hydroxide (LDH) nanoparticles. Our experimental data indicate that “IV-priming + SC-boosting” vaccination combination most efficiently inhibits the growth of early stage tumors, with the tumor volume reduced by >75-90 % in comparison with the control group. Based on these findings, a novel vaccination strategy, i.e. simultaneous IV and SC injection was proposed, which significantly delayed the progression of both early stage and advanced B16F10 tumors. Our current research for the first time correlates the vaccination route of nanovaccines to the anti-tumor therapeutic efficacy, and the highest efficacy of optimal vaccination combination (IV + SC) is benefited from that fact that IV priming quickly induces strong anti-tumor responses that are well sustained by subsequent SC boosting. Moreover, the simultaneous IV/SC vaccination potentially provides a novel vaccination strategy for enhanced immunotherapy of early stage and advanced tumors.

中文翻译：

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纳米疫苗快速诱导抗肿瘤免疫显着改善恶性肿瘤免疫治疗

摘要 肿瘤快速生长相对于免疫诱导缓慢的优势通常限制了癌症治疗疫苗的效率。许多功能化的微/纳米疫苗被证明可以增强癌症免疫治疗，但很少有研究将这些微/纳米疫苗的治疗功效与疫苗接种途径相关联，例如静脉注射 (IV)、皮下 (SC) 注射或它们的组合。在此，我们采用经典的“启动 + 加强”疫苗接种策略来研究纳米疫苗的四种疫苗接种组合（IV + IV、IV + SC、SC + IV 和 SC + SC）对携带 E 的小鼠的抗肿瘤治疗效果的影响。 .G7-OVA-淋巴瘤和B16F10-黑色素瘤。通过将抗原和 CpG 加载到层状双氢氧化物 (LDH) 纳米颗粒上来构建纳米疫苗。我们的实验数据表明，“IV-priming + SC-boosting”疫苗接种组合最有效地抑制了早期肿瘤的生长，与对照组相比，肿瘤体积减少了>75-90%。基于这些发现，提出了一种新的疫苗接种策略，即同时静脉注射和皮下注射，这显着延迟了早期和晚期 B16F10 肿瘤的进展。我们目前的研究首次将纳米疫苗的疫苗接种途径与抗肿瘤治疗效果联系起来，最佳疫苗接种组合（IV + SC）的最高疗效得益于这样一个事实，即 IV 引发迅速诱导强烈的抗肿瘤反应，被随后的 SC 提升很好地维持。而且，