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<p>Immunosuppression within the tumor microenvironment (TME) profoundly inhibits anti-tumor immunity, presenting a formidable challenge in cancer therapeutics. Despite this recognized obstacle, multi-targeted immunomodulatory strategies remain elusive. Here we developed a novel mRNA-lipid nanoparticle (LNP) vaccine designed to reprogram key cellular mediators of immune suppression within the TME, including C-C motif chemokine ligand 22 (CCL22), transforming growth factor-β (TGF-β), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Galectin-3, programmed cell death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase 1&#xa0;(IDO1), and arginase 1 (ARG1). This immunomodulatory vaccine was evaluated in a cohort of canines with spontaneous neoplasms, encompassing adrenal, hepatic, perianal, vulvar, and pulmonary malignancies. The vaccine demonstrated good tolerability, with only mild adverse events (Grade 1 anorexia, chills, and fatigue) observed in 25% of subjects (2/8). Remarkably, 75% of treated animals (6/8) achieved stable disease, with the median progression-free interval not yet reached a median follow-up of 168&#xa0;days post-treatment initiation. Two dogs experienced disease progression. The overall disease control rate was 75%. In addition, vaccine administration reversed hematological and biochemical abnormalities and alleviated paraneoplastic syndromes associated with these malignancies. These findings demonstrate that our mRNA-LNP vaccine effectively exerts anti-tumor effects across various cancer types, offering a promising strategy for enhancing anti-tumor immunity in both veterinary and human oncology.</p>

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Immunomodulatory vaccine demonstrates therapeutic efficacy across cancer types

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月31日

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  • Tiyun Han,
  • Guilai Liu,
  • Chenyi Bao,
  • Jian Zong,
  • Caiyi Fei,
  • Jing Li,
  • Shi Xu,
  • Qingbo Ma,
  • Yingjuan Qian

摘要

Immunosuppression within the tumor microenvironment (TME) profoundly inhibits anti-tumor immunity, presenting a formidable challenge in cancer therapeutics. Despite this recognized obstacle, multi-targeted immunomodulatory strategies remain elusive. Here we developed a novel mRNA-lipid nanoparticle (LNP) vaccine designed to reprogram key cellular mediators of immune suppression within the TME, including C-C motif chemokine ligand 22 (CCL22), transforming growth factor-β (TGF-β), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Galectin-3, programmed cell death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase 1 (IDO1), and arginase 1 (ARG1). This immunomodulatory vaccine was evaluated in a cohort of canines with spontaneous neoplasms, encompassing adrenal, hepatic, perianal, vulvar, and pulmonary malignancies. The vaccine demonstrated good tolerability, with only mild adverse events (Grade 1 anorexia, chills, and fatigue) observed in 25% of subjects (2/8). Remarkably, 75% of treated animals (6/8) achieved stable disease, with the median progression-free interval not yet reached a median follow-up of 168 days post-treatment initiation. Two dogs experienced disease progression. The overall disease control rate was 75%. In addition, vaccine administration reversed hematological and biochemical abnormalities and alleviated paraneoplastic syndromes associated with these malignancies. These findings demonstrate that our mRNA-LNP vaccine effectively exerts anti-tumor effects across various cancer types, offering a promising strategy for enhancing anti-tumor immunity in both veterinary and human oncology.