抗 CTLA-4 抗体淋巴给药与局部放疗相结合治疗实体瘤。

IF 5.7 2区 医学 Q1 Medicine
Cancer Science Pub Date : 2024-10-08 DOI:10.1111/cas.16369
Koki Takagi, Ariunbuyan Sukhbaatar, Yohei Inaba, Shiro Mori, Tetsuya Kodama
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引用次数: 0

摘要

放疗与免疫疗法相结合是一种很有前景的方法,临床试验表明,与单一疗法相比,放疗能显著提高实体瘤患者的生存率和反应率。由于抗CTLA-4抗体主要阻断淋巴结(LNs)中的免疫抑制信号,因此需要向淋巴系统高效给药。然而,免疫检查点抑制剂,尤其是抗CTLA-4目前都是静脉给药,导致其在控制实体瘤和抑制转移方面的疗效有限,而且给药方法尚未优化。在这里,我们展示了局部放疗和使用淋巴给药系统(LDDS)给药抗CTLA-4抗体的组合能抑制实体瘤和转移。我们在一种实体瘤模型中比较了基于淋巴给药系统的免疫疗法或放射免疫疗法与静脉给药的疗效,该模型是通过将骨肉瘤细胞皮下注射到LN肿胀的小鼠体内而建立的。携带肿瘤的小鼠被分为不同的组别(无治疗组、免疫治疗组(静脉注射或 LDDS)组、放射治疗组和放射免疫治疗组(静脉注射或 LDDS)组),并观察 28 天。免疫治疗采用累积剂量为10 mg/kg的抗CTLA-4单克隆抗体,放射治疗采用累积剂量为8 Gy的分次X射线照射。单用免疫疗法时,LDDS能轻微抑制肿瘤生长,但不能抑制远处转移。然而,与单纯放射治疗相比,放射免疫治疗可延缓肿瘤生长并抑制远处转移。特别是,LDDS组在T细胞介导的免疫活性方面取得了很高的肿瘤抑制效果,这表明LDDS在放射免疫疗法中的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A combination of lymphatic drug delivery of anti-CTLA-4 antibody and local radiotherapy for solid-tumor treatment.

The combination of radiotherapy and immunotherapy is a promising approach that has been shown in clinical trials to improve significantly survival and response rates compared with monotherapy against solid tumor. Since anti-CTLA-4 antibodies block immunosuppressive signals mainly in the lymph nodes (LNs), efficient drug delivery to the lymphatic system is desirable. However, the immune checkpoint inhibitors, especially anti-CTLA-4 are currently administered intravenously (i.v.), resulting in limited efficacy in controlling solid tumor and inhibiting metastases, and the method of administration has not been optimized. Here, we show that a combination of local radiotherapy and administration of anti-CTLA-4 antibodies using a lymphatic drug delivery system (LDDS) suppresses solid tumor and metastases. We compared the efficacy of LDDS-based immunotherapy or radioimmunotherapy with i.v. administration in a solid-tumor model created by subcutaneous inoculation into LN-swollen mice with osteosarcoma cells. Tumor-bearing mice were divided into various groups (no treatment, immunotherapy [i.v. or LDDS], radiotherapy, and radioimmunotherapy [i.v. or LDDS]) and were observed for 28 days. Immunotherapy was administered with a cumulative dose of 10 mg/kg of anti-CTLA-4 monoclonal antibody, and radiotherapy was administered with a cumulative 8 Gy of fractionated X-ray irradiation. For immunotherapy alone, LDDS provided slight tumor growth inhibition but did not inhibit distant metastasis. For radioimmunotherapy, however, tumor growth was delayed and distant metastasis was suppressed compared with radiotherapy alone. In particular, the LDDS group achieved a high tumor-suppressive effect with T cell-mediated immune activity, indicating the efficacy of LDDS in radioimmunotherapy.

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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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