Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, P. R. China.
College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, P. R. China.
Adv Healthc Mater. 2024 Jul;13(17):e2303690. doi: 10.1002/adhm.202303690. Epub 2024 May 2.
Cancer vaccines provide a potential strategy to cure patients. Their clinical utilization and efficacy is, however, limited by incomplete coverage of tumor neoantigens and unspecific and restricted activation of dendritic cells (DCs). Tumor cell lysates (TCLs) containing a broad spectrum of neoantigens, while are considered ideal in formulating personalized vaccines, induce generally poor antigen presentation and transient antitumor immune response. Here, intelligent polymersomal nanovaccines (PNVs) that quantitatively coload, efficiently codeliver, and responsively corelease TCL and CpG adjuvant to lymph node (LN) DCs are developed to boost antigen presentation and to induce specific and robust antitumor immunity. PNVs carrying CpG and ovalbumin (OVA) markedly enhance the maturation, antigen presentation, and downstream T cell activation ability of bone-marrow-derived dendritic cells and induce strong systemic immune response after tail base injection. Remarkably, PNVs carrying CpG and TCL cure 85% of B16-F10 melanoma-bearing mice and generate long-lasting anticancer immune memory at a low dose, protecting all cured mice from tumor rechallenge. These LN-directed PNVs being highly versatile and straightforward opens a new door for personalized cancer vaccines.
癌症疫苗提供了一种治愈患者的潜在策略。然而，它们的临床应用和疗效受到肿瘤新抗原覆盖不完全以及树突状细胞（DC）的非特异性和受限激活的限制。含有广泛新抗原的肿瘤细胞裂解物（TCL）虽然被认为是制定个性化疫苗的理想选择，但诱导的抗原呈递通常较差，且抗肿瘤免疫反应短暂。在这里，开发了智能聚合物纳米疫苗（PNV），定量共载、高效共递、响应性地将 TCL 和 CpG 佐剂释放到淋巴结（LN）DC 中，以增强抗原呈递并诱导特异性和强大的抗肿瘤免疫。携带 CpG 和卵清蛋白（OVA）的 PNV 显著增强了骨髓来源树突状细胞的成熟、抗原呈递和下游 T 细胞激活能力，并在尾部基部注射后引起强烈的全身免疫反应。值得注意的是，携带 CpG 和 TCL 的 PNV 治愈了 85%的 B16-F10 黑色素瘤荷瘤小鼠，并在低剂量下产生持久的抗癌免疫记忆，保护所有治愈的小鼠免受肿瘤再挑战。这些高度通用且简单的 LN 导向 PNV 为个性化癌症疫苗开辟了新的途径。
