Neoantigen mRNA vaccines and A₂A receptor antagonism: A strategy to enhance T cell immunity.

IF 4.1 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Human Vaccines & Immunotherapeutics Pub Date : 2025-12-01 Epub Date: 2025-01-30 DOI:10.1080/21645515.2025.2458936

Saber Imani, Parham Jabbarzadeh Kaboli, Ali Babaeizad, Mazaher Maghsoudloo

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引用次数: 0

Abstract

Although neo-antigen mRNA vaccines are promising for personalized cancer therapy, their effectiveness is often limited by the immunosuppressive tumor microenvironment (TME). The adenosine A₂A receptor (A₂AR) inhibits dendritic cell (DC) function and weakens antitumor T cell responses through hypoxia-driven mechanisms within the TME. This review explores a novel strategy combining neo-antigen mRNA vaccines with A₂AR antagonists (A₂ARi). By targeting A₂AR, this approach reduces TME-induced immunosuppression, enhances DC activation, and improves neo-antigen presentation. The review also discusses lipid nanoparticles (LNPs) to co-deliver A₂ARi and mRNA vaccines, optimizing their effectiveness. The integration of neo-antigen mRNA-LNPs with A₂ARi modulation offers a promising strategy to overcome immunosuppression, stimulate DC activation, and achieve precise anti-tumor responses with minimal off-target effects. This synergy represents significant progress in cancer immunotherapy, advancing the potential for personalized neoantigen therapies.

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尽管新抗原 mRNA 疫苗在个性化癌症治疗中大有可为，但其有效性往往受到免疫抑制性肿瘤微环境 (TME) 的限制。腺苷 A2A 受体（A2AR）会抑制树突状细胞（DC）的功能，并通过肿瘤微环境中的缺氧驱动机制削弱抗肿瘤 T 细胞的反应。本综述探讨了一种将新抗原 mRNA 疫苗与 A2AR 拮抗剂（A2ARi）相结合的新策略。通过靶向 A2AR，这种方法可减少 TME 诱导的免疫抑制、增强 DC 活化并改善新抗原呈递。综述还讨论了脂质纳米颗粒（LNPs）如何共同递送 A2ARi 和 mRNA 疫苗，从而优化其效果。将新抗原 mRNA-LNPs 与 A2ARi 调节相结合，为克服免疫抑制、刺激直流电活化、实现精确抗肿瘤反应并将脱靶效应降至最低提供了一种前景广阔的策略。这种协同作用代表了癌症免疫疗法的重大进展，推动了个性化新抗原疗法的发展潜力。

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来源期刊

Human Vaccines & Immunotherapeutics BIOTECHNOLOGY & APPLIED MICROBIOLOGY-IMMUNOLOGY

CiteScore

7.90

自引率

8.30%

发文量

489

审稿时长

3-6 weeks

期刊介绍： (formerly Human Vaccines; issn 1554-8619) Vaccine research and development is extending its reach beyond the prevention of bacterial or viral diseases. There are experimental vaccines for immunotherapeutic purposes and for applications outside of infectious diseases, in diverse fields such as cancer, autoimmunity, allergy, Alzheimer’s and addiction. Many of these vaccines and immunotherapeutics should become available in the next two decades, with consequent benefit for human health. Continued advancement in this field will benefit from a forum that can (A) help to promote interest by keeping investigators updated, and (B) enable an exchange of ideas regarding the latest progress in the many topics pertaining to vaccines and immunotherapeutics. Human Vaccines & Immunotherapeutics provides such a forum. It is published monthly in a format that is accessible to a wide international audience in the academic, industrial and public sectors.