Tumor tissues/cells are the best sources of antigens to prepare cancer vaccines. However, due to the difficulty of solubilization and delivery of water-insoluble antigens in tumor tissues/cells, including water-insoluble antigens into cancer vaccines and delivering such vaccines efficiently to antigen-presenting cells (APCs) remain challenging. To solve these problems, herein, water-insoluble components of tumor tissues/cells are solubilized by 8 m urea and thus whole components of micrometer-sized tumor cells are reasssembled into nanosized nanovaccines. To induce maximized immunization efficacy, various antigens are loaded both inside and on the surface of nanovaccines. By encapsulating both water-insoluble and water-soluble components of tumor tissues/cells into nanovaccines, the nanovaccines are efficiently phagocytosed by APCs and showed better therapeutic efficacy than the nanovaccine loaded with only water-soluble components in melanoma and breast cancer. Anti-PD-1 antibody and metformin can improve the efficacy of nanovaccines. In addition, the nanovaccines can prevent lung cancer (100%) and melanoma (70%) efficiently in mice. T cell analysis and tumor microenvironment analysis indicate that tumor-specific T cells are induced by nanovaccines and both adaptive and innate immune responses against cancer cells are activated by nanovaccines. Overall, this study demonstrates a universal method to make tumor-cell-based nanovaccines for cancer immunotherapy and prevention.

中文翻译：

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通过装载肿瘤组织或细胞的全细胞成分的纳米疫苗进行免疫治疗和预防癌症

肿瘤组织/细胞是制备癌症疫苗的最佳抗原来源。然而，由于水不溶性抗原在肿瘤组织/细胞中的溶解和递送困难，包括将水不溶性抗原导入癌症疫苗并将此类疫苗有效递送至抗原呈递细胞 (APC) 仍然具有挑战性。为了解决这些问题，本文将肿瘤组织/细胞的水不溶性成分溶解8 m尿素和微米级肿瘤细胞的全部成分被重新组装成纳米级纳米疫苗。为了使免疫效果最大化，纳米疫苗的内部和表面都装载了各种抗原。通过将肿瘤组织/细胞的水不溶性和水溶性成分封装到纳米疫苗中，纳米疫苗可被 APCs 有效吞噬，并且在黑色素瘤和乳腺癌中显示出比仅加载水溶性成分的纳米疫苗更好的治疗效果。抗PD-1抗体和二甲双胍可以提高纳米疫苗的疗效。此外，纳米疫苗可以有效预防小鼠的肺癌（100%）和黑色素瘤（70%）。T 细胞分析和肿瘤微环境分析表明，肿瘤特异性 T 细胞由纳米疫苗诱导，针对癌细胞的适应性和先天免疫反应均由纳米疫苗激活。总体而言，这项研究展示了一种用于制造用于癌症免疫治疗和预防的基于肿瘤细胞的纳米疫苗的通用方法。