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利用免疫修饰碳纳米管进行光疗,增强转移性乳腺癌的检查点阻断。

Phototherapy using immunologically modified carbon nanotubes to potentiate checkpoint blockade for metastatic breast cancer.

机构信息

Interventional Therapy Department, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Biophotonics Research Laboratory, Center for Interdisciplinary Biomedical Education and Research, College of Mathematics and Science, University of Central Oklahoma, Edmond, OK, USA.

Biophotonics Research Laboratory, Center for Interdisciplinary Biomedical Education and Research, College of Mathematics and Science, University of Central Oklahoma, Edmond, OK, USA; Department of Oncology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.

出版信息

Nanomedicine. 2019 Jun;18:44-53. doi: 10.1016/j.nano.2019.02.009. Epub 2019 Mar 4.

Abstract

Metastasis is the major cause of cancer-death. Checkpoint inhibition shows great promise as an immunotherapeutic treatment for cancer patients. However, most currently available checkpoint inhibitors have low response rates. To augment the antitumor efficacy of checkpoint inhibitors, such as CTLA-4 antibodies, a single-walled carbon nanotube (SWNT) modified by a novel immunoadjuvant, glycated chitosan (GC), was used for the treatment of metastatic mammary tumors in mice. We treated the primary tumors by intratumoral administration of SWNT-GC, followed with irradiation with a 1064-nm laser to achieve local ablation through photothermal therapy (PTT). The treatment induced a systemic antitumor immunity which inhibited lung metastasis and prolonged the animal survival time of treated. Combining SWNT-GC-laser treatment with anti-CTLA-4 produced synergistic immunomodulatory effects and further extended the survival time of the treated mice. The results showed that the special combination, PTT + SWNT-GC + anti-CTLA, could effectively suppress primary tumors and inhibit metastases, providing a new treatment strategy for metastatic cancers.

摘要

转移是癌症死亡的主要原因。检查点抑制作为癌症患者的一种免疫治疗方法具有很大的前景。然而,大多数现有的检查点抑制剂的反应率较低。为了增强检查点抑制剂(如 CTLA-4 抗体)的抗肿瘤疗效,使用了一种新型免疫佐剂——糖化壳聚糖(GC)修饰的单壁碳纳米管(SWNT)来治疗小鼠的转移性乳腺肿瘤。我们通过瘤内给予 SWNT-GC 来治疗原发性肿瘤,然后用 1064nm 激光照射以实现通过光热疗法(PTT)进行局部消融。该治疗诱导了全身性抗肿瘤免疫,抑制了肺转移并延长了治疗动物的存活时间。将 SWNT-GC-激光治疗与抗 CTLA-4 联合使用产生了协同的免疫调节作用,并进一步延长了治疗小鼠的存活时间。结果表明,这种特殊的联合治疗(PTT+SWNT-GC+抗 CTLA)可有效抑制原发性肿瘤并抑制转移,为转移性癌症提供了一种新的治疗策略。

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