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首页> 外文期刊>Advanced Functional Materials >Combination of Bacterial-Photothermal Therapy with an Anti-PD-1 Peptide Depot for Enhanced Immunity against Advanced Cancer
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Combination of Bacterial-Photothermal Therapy with an Anti-PD-1 Peptide Depot for Enhanced Immunity against Advanced Cancer

机译：细菌光热疗法与抗PD-1肽库的组合，可增强抗晚期癌症的免疫力

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Photothermal therapy (PTT) is a promising cancer treatment, but it has so far proven successful only with relatively small subcutaneous tumors in animal models. Treating larger tumors (approximate to 200 mm(3)) is challenging because most PTT materials do not efficiently reach the hypoxic, avascular center of tumors, and the immunosuppressive tumor microenvironment prevents T cells from fighting against residual tumor cells, thereby allowing recurrence and metastasis. Here, the widely used PTT material polydopamine is coated on the surface of the facultative anaerobe Salmonella VNP20009, which can penetrate deep into larger tumors. The coated bacteria are intravenously injected followed by near-infrared laser irradiation at the tumor site, combined with a local inoculation of phospholipid-based phase separation gel containing the anti-programmed cell death-1 peptide AUNP-12. The gel releases AUNP-12 sustainably during 42 days, maintaining the tumor microenvironment as immunopermissive. Using a mouse model of melanoma, this triple combination of biotherapy, PTT, and sustainable programmed cell death-1 (PD-1) blockade shows high efficiency on eliciting robust antitumor immune responses and eliminating relatively large tumors in 50% of animals within 80 days. Thus, the results shed new light on a previously unrecognized immunological facet of bacteria-mediated therapy, and this innovative triple therapy may be a powerful cancer immunotherapy tool.
机译：光热疗法（PTT）是一种有前途的癌症治疗方法，但到目前为止，仅在动物模型中皮下相对较小的肿瘤中，光热疗法才被证明是成功的。因为大多数PTT材料不能有效地到达肿瘤的缺氧性，无血管中心，而且免疫抑制性肿瘤微环境阻止T细胞与残留的肿瘤细胞竞争，从而治疗复发和转移，所以治疗较大的肿瘤（约200 mm（3））具有挑战性。 。在这里，广泛使用的PTT材料聚多巴胺被涂在兼性厌氧菌沙门氏菌VNP20009的表面上，可以深入到较大的肿瘤中。将包被的细菌静脉内注射，然后在肿瘤部位进行近红外激光照射，并与含有抗编程性细胞死亡1肽AUNP-12的磷脂基相分离凝胶进行局部接种。凝胶在42天之内可持续释放AUNP-12，使肿瘤微环境保持免疫状态。使用黑色素瘤的小鼠模型，这种生物疗法，PTT和可持续程序性细胞死亡1（PD-1）阻断的三重组合显示了在80天内能有效引发强烈的抗肿瘤免疫反应并消除50％的动物相对较大的肿瘤的高效率。因此，该结果为细菌介导的治疗方法以前无法识别的免疫学方面提供了新的思路，而这种创新的三联疗法可能是一种强大的癌症免疫治疗工具。

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