疫苗是癌症免疫治疗中最有前景的策略之一，然而，迄今为止还没有达到显著临床疗效的治疗性癌症疫苗。主要的限制因素包括肿瘤发展的免疫抑制和逃逸机制以及疫苗的诱导强大抗肿瘤免疫的能力不足。本研究旨在开发基于膜的仿生纳米疫苗策略，并调查利用免疫原性细胞死亡（ICD）所衍生的独特免疫刺激机制，以及在疫苗设计中同时进行突出显示的肿瘤抗原和广泛的膜相关肿瘤抗原的纳米尺度传递的免疫学结果。使用MIT 和 CUR 混合处理体外培养的TC-1 肿瘤细胞以诱导ICD，然后用HPV16 E744-62 肽装载的壳聚糖（CS）包裹的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒与准备的ICD 肿瘤细胞膜（IM）装饰；进一步，将IM 装饰的纳米颗粒与三磷酸腺苷（ATP）嵌入海藻酸钠（ALG）水凝胶中，然后在体外和体内评估免疫学特征和治疗效力。纳米疫苗显著刺激体外的DC 细胞迁移、抗原摄取和成熟，提高抗原溶酶体逃逸，在体内促进注射部位的保留和淋巴结中的肿瘤抗原积累。在皮下移植的TC-1 肿瘤模型中，纳米疫苗的治疗免疫诱导了显著的抗肿瘤免疫力。本研究为肿瘤疫苗的开发提供了一种策略。© 2023。BioMed Central有限公司，斯普林格自然出版集团的一部分。

Vaccine is one of the most promising strategies for cancer immunotherapy; however, there are no therapeutic cancer vaccine achieving significant clinical efficacy till now. The main limiting factors include the immune suppression and escape mechanisms developed by tumor and not enough capacity of vaccines to induce a vigorous anti-tumor immunity. This study aimed to develop a strategy of membrane-based biomimetic nanovaccine and investigate the immunological outcomes of utilizing the unique immunostimulatory mechanisms derived of immunogenic cell death (ICD) and of fulfilling a simultaneous nanoscale delivery of a highlighted tumor antigen and broad membrane-associated tumor antigens in the vaccine design. TC-1 tumor cells were treated in vitro with a mixture of mitoxantrone and curcumin for ICD induction, and then chitosan (CS)-coated polylactic co-glycolic acid (PLGA) nanoparticles loaded with HPV16 E744-62 peptides were decorated with the prepared ICD tumor cell membrane (IM); further, the IM-decorated nanoparticles along with adenosine triphosphate (ATP) were embedded with sodium alginate (ALG) hydrogel, And then, the immunological features and therapeutic potency were evaluated in vitro and in vivo. The nanovaccine significantly stimulated the migration, antigen uptake, and maturation of DCs in vitro, improved antigen lysosome escape, and promoted the retention at injection site and accumulation in LNs of the tumor antigen in vivo. In a subcutaneously grafted TC-1 tumor model, the therapeutic immunization of nanovaccine elicited a dramatical antitumor immunity. This study provides a strategy for the development of tumor vaccines.© 2023. BioMed Central Ltd., part of Springer Nature.