Niimura Mayumi, Sakamoto Yasuhisa, Shimoda Mayuko, Harada Narumi, Maeda Ayato, Wada Shiho, Murata Koki, Thinyakul Chanida, Liu Saisai, Ohara Haruka, Iwamoto Asuka, Kanamori Yohei, Nita Akihiro, Wakao Masahiro, Suda Yasuo, Oshiumi Hiroyuki, Hayashi Tomoko, Carson Dennis A, Shinchi Hiroyuki, Moroishi Toshiro
Department of Molecular and Medical Pharmacology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Division of Cellular Dynamics, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Commun Med (Lond). 2025 Aug 29;5(1):378. doi: 10.1038/s43856-025-01102-3.
Cancer immunotherapy, particularly using immune checkpoint inhibitors, has revolutionized cancer treatment; however, its efficacy remains limited to a subset of patients. Nanoparticles have potential in cancer treatment because they offer advantages such as biocompatibility, greater stability, and precise targeting capabilities.
We synthesized an integrated glyco-nanovaccine (iGN) comprising gold nanoparticles conjugated with a synthetic Toll-like receptor 7 (TLR7) ligand, sugar chains, and peptide antigens for cancer immunotherapy. The potential of iGN was investigated using a therapeutic animal model.
In murine models, iGN effectively induces antigen-specific cytotoxic T cells, demonstrating prophylactic and therapeutic efficacy against tumor growth. iGN stimulates antigen-presenting cells via the TLR7-MYD88 pathway, enhancing antigen presentation and priming of cytotoxic T cells. Combination therapy with iGN and anti-PD-1 antibodies improves survival of tumor-bearing mice.
These findings underscore the potential of iGN as a strategy to enhance cancer immunotherapy, particularly when used in combination with immune checkpoint blockade, to bolster anti-tumor immune responses and improve therapeutic outcomes.
癌症免疫疗法,尤其是使用免疫检查点抑制剂的疗法,已经彻底改变了癌症治疗方式;然而,其疗效仍然仅限于一部分患者。纳米颗粒在癌症治疗中具有潜力,因为它们具有生物相容性、更高的稳定性和精确的靶向能力等优势。
我们合成了一种整合糖纳米疫苗(iGN),其由与合成的Toll样受体7(TLR7)配体、糖链和肽抗原偶联的金纳米颗粒组成,用于癌症免疫治疗。使用治疗性动物模型研究了iGN的潜力。
在小鼠模型中,iGN有效诱导抗原特异性细胞毒性T细胞,显示出对肿瘤生长的预防和治疗效果。iGN通过TLR7-MYD88途径刺激抗原呈递细胞,增强抗原呈递和细胞毒性T细胞的致敏。iGN与抗PD-1抗体联合治疗可提高荷瘤小鼠的生存率。
这些发现强调了iGN作为增强癌症免疫治疗策略的潜力,特别是与免疫检查点阻断联合使用时,可增强抗肿瘤免疫反应并改善治疗效果。