Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China.
Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China.
Acta Biomater. 2021 Oct 1;133:257-267. doi: 10.1016/j.actbio.2021.08.014. Epub 2021 Aug 15.
Combined cell vaccines of tumor whole cells and dendritic cells (DCs) provide an effective individualized immunotherapy for malignant tumors. We propose an innovative strategy termed "biomaterial-mediated combined cell vaccines for immunotherapy," which combines tumor cell and DC vaccines with a cyclodextrin-polyethylene glycol hydrogel and a cytosine-phosphate-guanine (CpG) nanoadjuvant. The nanoadjuvant promotes antigen presentation and amplifies immune-eliciting potency by co-delivery of antigens and adjuvants. The hydrogel scaffold provides a better growth microenvironment for injected exogenous DCs and recruits endogenous DCs to maintain their viability for synergistic effect. The results indicated that, relative to live tumor cells, the immunogenically dying tumor cells activated DC maturation effectively with the auxiliary effect of immune adjuvant CpG nanoparticles. The increased T cell percentage, proliferation ability, cytokine secretion, and cytotoxic effect revealed the enhanced immunogenicity of the combined cell vaccines. The combined hydrogel/nanoadjuvant system showed the best efficiency in inhibiting tumor growth. Moreover, vaccination with a single dose of hydrogel-based combined vaccines significantly delayed the development of tumors. The biomaterial-mediated combined cell vaccines remarkably increased the infiltration of effector T cells, alleviated the intratumoral immunosuppressive microenvironment, and maximized the immune effect of the vaccines, thus improving cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Cell-based vaccines, including tumor whole-cell vaccine or DC vaccine, have attracted wide attention as an effective method for cancer immunotherapy. However, it is difficult to gain satisfactory outcomes in clinical trials because of the low immunogenicity of tumor whole cell vaccine and the short-term survival of transferred DC vaccine. Therefore, improving the ability of cell-based vaccines to induce a strong and durable immune response is the primary objective for vaccine development. Biomaterial-mediated combined cell vaccines is an innovative strategy for cancer immunotherapy. The combined hydrogel/ nanoadjuvant system comprises immunogenically dying tumor cells, DCs, and nanoadjuvants. Nanoadjuvant-loaded immunogenically dying tumor cells can induce efficient immune response as the tumor cell vaccine. The hydrogel-based combined tumor cell/DC vaccine could be used for individualized immunotherapy.
肿瘤全细胞和树突状细胞（DC）联合细胞疫苗为恶性肿瘤提供了有效的个体化免疫治疗。我们提出了一种创新策略，称为“基于生物材料的联合细胞疫苗免疫治疗”，该策略将肿瘤细胞和 DC 疫苗与环糊精-聚乙二醇水凝胶和胞嘧啶-磷酸-鸟嘌呤（CpG）纳米佐剂结合使用。纳米佐剂通过共递送抗原和佐剂来促进抗原呈递并放大免疫激发效力。水凝胶支架为注射的外源性 DC 提供了更好的生长微环境，并募集内源性 DC 以维持其活力以产生协同作用。结果表明，与活肿瘤细胞相比，免疫原性死亡的肿瘤细胞在免疫佐剂 CpG 纳米颗粒的辅助作用下有效地激活了 DC 成熟。增加的 T 细胞百分比、增殖能力、细胞因子分泌和细胞毒性作用揭示了联合细胞疫苗的增强免疫原性。联合水凝胶/纳米佐剂系统在抑制肿瘤生长方面显示出最佳效率。此外，单次剂量的水凝胶基联合疫苗接种显著延迟了肿瘤的发展。基于生物材料的联合细胞疫苗显著增加了效应 T 细胞的浸润，减轻了肿瘤内免疫抑制微环境，并最大限度地提高了疫苗的免疫效果，从而改善了癌症免疫治疗。
基于细胞的疫苗，包括肿瘤全细胞疫苗或 DC 疫苗，作为癌症免疫治疗的有效方法引起了广泛关注。然而，由于肿瘤全细胞疫苗的免疫原性低和转导的 DC 疫苗的短期存活，临床试验中难以获得令人满意的结果。因此，提高基于细胞的疫苗诱导强烈和持久免疫反应的能力是疫苗开发的主要目标。基于生物材料的联合细胞疫苗是癌症免疫治疗的一种创新策略。联合水凝胶/纳米佐剂系统由免疫原性死亡的肿瘤细胞、DC 和纳米佐剂组成。负载纳米佐剂的免疫原性死亡的肿瘤细胞可作为肿瘤细胞疫苗诱导有效的免疫反应。基于水凝胶的联合肿瘤细胞/DC 疫苗可用于个体化免疫治疗。
