Department of Diagnostic Radiology, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore.
Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Cancer Res. 2024 Nov 15;84(22):3709-3711. doi: 10.1158/0008-5472.CAN-24-2905.
A range of advanced nanovaccines (NV) combined with immunotherapies has recently emerged for treating malignant tumors and has demonstrated promising tumor-suppressive effects. Nevertheless, their effectiveness is often limited by immunosuppression within the tumor microenvironment. To overcome this challenge, new approaches for NV development are required to improve antigen cross-presentation and to remodel the tumor microenvironment. In this issue of Cancer Research, Zhou and colleagues have developed a photo-enhanceable inflammasome-activating nanovaccine (PIN) designed for precise, in situ delivery of a tumor antigen and a hydrophobic small molecule that activates the NLRP3 inflammasome pathway. Near infrared light exposure enables the accumulation of PINs at tumor sites by inducing a photo-triggered charge reversal in the BODIPY-modified PAMAM nanocarrier. Systemic administration of PINs resulted in effective intratumoral activation of the NLRP3 inflammasome and antigen cross-presentation in antigen-presenting cells upon light exposure, leading to enhanced immune responses through increased proinflammatory cytokine production without significant systemic toxicity. Importantly, PINs also enhanced the efficacy of immune checkpoint blockade and promoted the development of long-term immune memory in mouse models of melanoma and hepatocellular carcinoma. Overall, inflammasome-activating NVs represent a cancer immunotherapy strategy by harnessing the innate immune system to achieve robust responses against tumors. Ongoing research and development are crucial to addressing current limitations and advancing this innovative technology toward clinical application. See related article by Zhou et al., p. 3834.
一系列先进的纳米疫苗（NV）与免疫疗法相结合，最近已被用于治疗恶性肿瘤，并显示出有希望的肿瘤抑制作用。然而，它们的有效性往往受到肿瘤微环境中免疫抑制的限制。为了克服这一挑战，需要开发新的 NV 方法来提高抗原交叉呈递和重塑肿瘤微环境。在本期《癌症研究》中，Zhou 及其同事开发了一种光增强的炎症小体激活纳米疫苗（PIN），旨在精确原位递送达肿瘤抗原和激活 NLRP3 炎症小体途径的疏水分子。近红外光暴露通过在 BODIPY 修饰的 PAMAM 纳米载体中诱导光触发电荷反转，使 PIN 聚集在肿瘤部位。PIN 的全身给药导致 NLRP3 炎症小体在光照下在抗原呈递细胞中有效激活和抗原交叉呈递，通过增加促炎细胞因子的产生增强免疫反应，而没有明显的全身毒性。重要的是，PIN 还增强了免疫检查点阻断的疗效，并在黑色素瘤和肝细胞癌的小鼠模型中促进了长期免疫记忆的发展。总体而言，激活炎症小体的 NV 代表了一种癌症免疫治疗策略，利用先天免疫系统实现对肿瘤的强大反应。正在进行的研究和开发对于解决当前的局限性和将这项创新技术推向临床应用至关重要。请参阅 Zhou 等人的相关文章，第 3834 页。
