While cancer immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors. We report that nanodiscs administered via the subcutaneous (SC) or intramuscular (IM) routes were well tolerated in mice without any signs of toxicity. The SC route significantly enhanced nanoparticle delivery to draining lymph nodes, improved nanodisc uptake by antigen-presenting cells, and generated 7-fold higher frequency of neoantigen-specific T cells, compared with the IM route. Importantly, when mice bearing advanced B16F10 melanoma tumors were treated with nanodiscs plus anti-PD-1 and anti-CTLA-4 IgG therapy, the combination immunotherapy exerted potent antitumor efficacy, leading to eradication of established tumors in ∼60% of animals. These results demonstrate nanodiscs customized with patient-specific tumor neoepitopes as a safe and powerful vaccine platform for immunotherapy against advanced cancer.

中文翻译：

---

皮下注射新抗原的纳米盘疫苗，用于联合癌症免疫治疗

尽管癌症免疫疗法为患者提供了新的令人兴奋的治疗选择，但迫切需要能够与免疫检查点阻滞剂协同作用并提高患者反应率的新策略。我们已经开发了基于合成高密度脂蛋白的个性化疫苗纳米光盘平台，用于共同递送免疫刺激剂和肿瘤抗原，包括肿瘤特异性新抗原。在这里，我们检查了针对已建立的肿瘤的纳米光盘疫苗接种的途径，安全性和治疗效果。我们报告通过小鼠的皮下（SC）或肌内（IM）途径管理的纳米光盘具有很好的耐受性，没有任何毒性迹象。SC途径显着增强了纳米颗粒向引流淋巴结的递送，改善了抗原呈递细胞对纳米盘的吸收，与IM路径相比，新抗原特异性T细胞的产生频率高7倍。重要的是，当用纳米碟片加上抗PD-1和抗CTLA-4 IgG疗法治疗患有晚期B16F10黑色素瘤肿瘤的小鼠时，联合免疫疗法发挥了强大的抗肿瘤功效，从而在约60％的动物中根除了已建立的肿瘤。这些结果表明，用患者特异性肿瘤新表位定制的纳米光盘是一种安全有效的针对晚期癌症的免疫疗法疫苗平台。导致约60％的动物根除已建立的肿瘤。这些结果表明，用患者特异性肿瘤新表位定制的纳米光盘是一种安全有效的针对晚期癌症的免疫疗法疫苗平台。导致约60％的动物根除已建立的肿瘤。这些结果表明，用患者特异性肿瘤新表位定制的纳米光盘是一种安全有效的针对晚期癌症的免疫疗法疫苗平台。