研究动态
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化疗诱导的纳米疫苗通过实现免疫原性等效性以提高癌症化疗免疫治疗效果。

Chemotherapy-induced nanovaccines implement immunogenicity equivalence for improving cancer chemoimmunotherapy.

发表日期:2023 Aug 21
作者: Rui Li, Yuhao Hao, Kyle Roche, Guiyuan Chen, Wen Pan, Andrew Z Wang, Yuanzeng Min
来源: Cellular & Molecular Immunology

摘要:

美国食品和药物管理局(FDA)已经批准了多种化疗联合免疫治疗药物,用于治疗各种癌症。化疗有潜力通过诱导肿瘤细胞的免疫原性细胞死亡(ICD)、促进肿瘤相关抗原(TAA)、肿瘤特异性抗原(TSA)和损伤相关分子模式(DAMP)的释放,以及通过肿瘤减量疗法破坏免疫抑制微环境,来提高免疫治疗的有效性。然而,化疗药物的全身给药会带来系统性免疫抑制的副作用,从而减弱抗癌免疫反应,这一内在矛盾值得在化疗联合免疫治疗中进一步探索。在此,我们提出了化疗免疫等效性的假设,即体外化疗药物诱导的免疫原性抗原和DAMP可以随后纳入纳米疫苗中,与体内经过全身化疗治疗的肿瘤相比,纳米疫苗将具有相当的免疫刺激潜力。蛋白质组分析证实了我们的纳米疫苗含有TAA、TSA和DAMP。我们观察到接受抗-PD-1和化疗诱导的纳米疫苗治疗的肿瘤小鼠的治疗结果得到了改善。此外,我们证明了用纳米疫苗替代长期化疗在化疗联合免疫治疗中的可行性。我们的纳米疫苗策略将成为个体化医学中制定癌症疫苗的普遍选择。版权所有 © 2023 Elsevier Ltd. 保留所有权利。
Several chemoimmunotherapies have been approved by the FDA for the treatment of various cancers. Chemotherapy has the potential to improve the efficacy of immunotherapy by inducing immunogenic cell death (ICD) of tumor cells, promoting the release of tumor associated antigens (TAAs), tumor specific antigens (TSAs) and damage associated molecular patterns (DAMPs), and disrupting immunosuppressive microenvironments by tumor debulking. Unfortunately, systemic administration of chemotherapeutics carries side effects of blunting anti-cancer immune response through systemic immunosuppression, which deserves to be explored as an inner contradiction in chemoimmunotherapy. Here, we proposed the hypothesis of "immunogenicity equivalence" in chemoimmunotherapy that chemotherapeutics-induced immunogenic antigens and DAMPs in vitro that can subsequently be incorporated into nanovaccines, which will possess comparable immunostimulatory potential when compared to tumors treated with systemic chemotherapy in vivo. The proteomic analysis confirmed that our nanovaccines contained TAAs, TSAs and DAMPs. Improvement in treatment outcomes in tumor-bearing mice receiving anti-PD-1 and chemotherapy-induced nanovaccines was then observed. Furthermore, we demonstrated the feasibility of replacing long-term chemotherapy with nanovaccines in chemoimmunotherapy. Our nanovaccine strategy would be a general choice for formulating cancer vaccines in personalized medicine.Copyright © 2023 Elsevier Ltd. All rights reserved.