State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Nat Commun. 2023 Jul 26;14(1):4505. doi: 10.1038/s41467-023-40207-y.
The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.
整体肿瘤细胞疫苗(TCV)的治疗效果有限,这延迟了它们在临床上转化为个性化免疫疗法的进程。在这里,我们开发了一种基于光热纳米颗粒负载肿瘤细胞的 TCV 平台,该平台可以合理应用于多种肿瘤类型,按需增强抗肿瘤免疫反应,抑制肿瘤生长。在制造过程中,近红外(NIR)激光照射的温和光热加热可诱导载纳米颗粒的肿瘤细胞表达热休克蛋白作为内源性佐剂。在荷瘤小鼠背部进行单次接种后,非侵入性的 NIR 激光照射进一步在接种部位引起温和的热疗,促进树突状细胞的募集、激活和抗原呈递。使用我们称之为肿瘤生长率波动的指标,我们确定了合适的照射方案(包括优化的照射间隔和次数)。该 TCV 平台可实现对免疫反应的按需 NIR 调控,我们针对模拟多种临床情况的六种小鼠模型展示了强大的治疗效果,包括基于人源化小鼠和患者来源的肿瘤异种移植模型。
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