Polymer Nanoparticle-Mediated Delivery of Oxidized Tumor Lysate-Based Cancer Vaccines
Polymer Nanoparticle-Mediated Delivery of Oxidized Tumor Lysate-Based Cancer Vaccines
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DOI：
10.1002/mabi.202100356
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发表时间：
2021-12-06
影响因子：
4.6
通讯作者：
Klok, Harm-Anton
中科院分区：
文献类型：
--
作者：
Berti, Cristiana;Graciotti, Michele;Klok, Harm-Anton
癌症疫苗接种是对抗癌症的有力策略。一个非常有吸引力的方法来启动免疫系统对抗癌细胞涉及使用肿瘤裂解物作为抗原来源。肿瘤裂解物的免疫原性可以通过用次氯酸处理进一步增强。这项研究探索了聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒来增强氧化肿瘤裂解物向树突状细胞的递送。使用人供体来源的树突状细胞，发现与使用游离肿瘤裂解物相比，使用PLGA纳米颗粒增强了抗原摄取和树突状细胞成熟。活化的树突状细胞刺激自体外周血单核细胞（PBMC）的能力通过将PBMC与A375黑素瘤细胞共培养来体外评估。该实验的活细胞成像分析突出了纳米颗粒介导的基于树突细胞的疫苗接种方法的潜力。最后，在使用B16 F10荷瘤C57 BL/6 J小鼠的治疗性疫苗接种研究中体内评价PLGA纳米颗粒制剂的功效。用基于聚合物纳米颗粒的氧化肿瘤裂解物制剂攻击的动物存活长达50天，而接受相应的基于游离氧化肿瘤裂解物的疫苗的组最多存活41天。
Cancer vaccination is a powerful strategy to combat cancer. A very attractive approach to prime the immune system against cancer cells involves the use of tumor lysate as antigen source. The immunogenicity of tumor lysate can be further enhanced by treatment with hypochlorous acid. This study explores poly(lactic-co-glycolic acid) (PLGA) nanoparticles to enhance the delivery of oxidized tumor lysate to dendritic cells. Using human donor-derived dendritic cells, it is found that the use of PLGA nanoparticles enhances antigen uptake and dendritic cell maturation, as compared to the use of the free tumor lysate. The ability of the activated dendritic cells to stimulate autologous peripheral blood mononuclear cells (PBMCs) is assessed in vitro by coculturing PBMCs with A375 melanoma cells. Live cell imaging analysis of this experiment highlights the potential of nanoparticle-mediated dendritic-cell-based vaccination approaches. Finally, the efficacy of the PLGA nanoparticle formulation is evaluated in vivo in a therapeutic vaccination study using B16F10 tumor-bearing C57BL/6J mice. Animals that are challenged with the polymer nanoparticle-based oxidized tumor lysate formulation survive for up to 50 days, in contrast to a maximum of 41 days for the group that receives the corresponding free oxidized tumor lysate-based vaccine.