Miura Risako, Sawada Shin-Ichi, Mukai Sada-Atsu, Sasaki Yoshihiro, Akiyoshi Kazunari
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University A3-317 Kyotodaigaku Katsura, Nishikyo-ku Kyoto 615-8510 Japan
RSC Adv. 2020 Feb 25;10(14):8074-8079. doi: 10.1039/c9ra10066k. eCollection 2020 Feb 24.
Therapeutic strategies for cancer involving immune checkpoint inhibitors (ICIs) have been gaining widespread attention, but their efficacy remains limited. Thus, combination of ICI therapies with other therapeutic modalities may be required to improve their outcomes. In this study, we examined the improved efficacy of a CHP nanogel-based vaccine delivery system after combination with ICI therapy. For this, we evaluated the therapeutic efficacy of combining an anti-PD-1 antibody as an ICI with an OVA antigen-complexed CHP nanogel vaccine delivery system in a mouse E.G7-OVA tumor model. Mice were subcutaneously inoculated with E.G7-OVA tumor cells on one side of the back, and subcutaneously injected with OVA or the OVA/CHP nanogel vaccine on the other side of the back. Anti-PD-1 antibody was administered at defined intervals. Tumor volume, immune responses, and tumor-infiltrating cells were evaluated. Mice treated with OVA vaccine alone showed weak tumor suppression compared with untreated control mice. Mice receiving combined OVA/CHP nanogel vaccine and anti-PD-1 antibody therapy exhibited strong tumor growth suppression and markedly improved survival, suggesting that PD-1 signaling blockade by the anti-PD-1 antibody enhanced the anti-tumor efficacy of the OVA vaccine. Furthermore, tumor-infiltrating cells and immune responses were increased in the combined therapy group. No serious side effects were observed for any of the treatments. Taken together, the immune system activation induced by the CHP nanogel vaccine was synergistically enhanced by the anti-PD-1 antibody. The present findings suggest the potential for enhanced therapeutic efficacy by combining the CHP nanogel vaccine delivery system with ICI therapy for various cancer types.
涉及免疫检查点抑制剂（ICI）的癌症治疗策略已受到广泛关注，但其疗效仍然有限。因此，可能需要将ICI疗法与其他治疗方式联合使用以改善治疗效果。在本研究中，我们检测了基于CHP纳米凝胶的疫苗递送系统与ICI疗法联合使用后疗效的改善情况。为此，我们在小鼠E.G7-OVA肿瘤模型中评估了将抗PD-1抗体作为ICI与OVA抗原复合的CHP纳米凝胶疫苗递送系统联合使用的治疗效果。小鼠在背部一侧皮下接种E.G7-OVA肿瘤细胞，并在背部另一侧皮下注射OVA或OVA/CHP纳米凝胶疫苗。按规定间隔给予抗PD-1抗体。评估肿瘤体积、免疫反应和肿瘤浸润细胞。与未治疗的对照小鼠相比，单独用OVA疫苗治疗的小鼠显示出较弱的肿瘤抑制作用。接受OVA/CHP纳米凝胶疫苗和抗PD-1抗体联合治疗的小鼠表现出强烈的肿瘤生长抑制作用且存活率显著提高，这表明抗PD-1抗体对PD-1信号的阻断增强了OVA疫苗的抗肿瘤疗效。此外，联合治疗组的肿瘤浸润细胞和免疫反应增加。任何治疗均未观察到严重的副作用。综上所述，抗PD-1抗体协同增强了CHP纳米凝胶疫苗诱导的免疫系统激活。本研究结果表明，将CHP纳米凝胶疫苗递送系统与ICI疗法联合用于各种癌症类型具有提高治疗效果的潜力。
