Optimal radiation dose to induce an abscopal effect by combining carbon-ion radiotherapy and anti-CTLA4 antibody

IF 4.8 2区医学 Q1 Biochemistry, Genetics and Molecular Biology

Neoplasia Pub Date : 2025-02-01 DOI:10.1016/j.neo.2024.101099

Liqiu Ma , Yang Li , Yoshimitsu Sakamoto , Lin Xie , Saaya Suzuki , Yukari Yoshida , Li Sui , Gang Guo , Jialing Wen , Wangcai Ren , Kazuhiro Kakimi , Kensuke Osada , Akihisa Takahashi , Takashi Shimokawa

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引用次数: 0

Abstract

Background and purpose

Although carbon-ion radiotherapy (CIRT) has led to good outcomes, controlling metastasis is still crucial for improving overall survival. This study aimed to evaluate the effectiveness of by two combinations, one of CIRT and anti-CTLA4 antibody, the other of CIRT and anti-PD-1 antibody, applied at different radiation doses for distal tumour and metastasis suppression.

Materials and methods

Murine cancer cells (colon carcinoma Colon-26 cells for experiments and osteosarcoma LM8 cells for verification) were grafted into both sides of the hind legs of syngeneic mice. Right-side tumours were irradiated with 3 Gy or 10 Gy CIRT while the left-side tumours were not irradiated, followed by the administration of the anti-CTLA4 antibody or anti-PD-1 antibody. The diameter of the tumours in both legs was measured 3 times per week after irradiation. The number of pulmonary metastases was evaluated within 3 weeks after irradiation.

Results

Compared with the control group, the high-dose group showed promising anti-cancer benefits in terms of both irradiated tumours and lung metastasis, but neither 10 Gy CIRT combined with the anti-CTLA4 antibody nor 10 Gy CIRT combined with the anti-PD-1 antibody suppressed the growth of distant unirradiated tumours. In the low-dose group, the effect on primary tumour control was slightly weaker than that in the high-dose treatment group, but significant suppressive effects on both distant unirradiated tumours and metastases were observed following 3 Gy CIRT combined with anti-CTLA4 antibody treatment. Specifically, the volume of distant unirradiated tumours decreased by 40 % compared with that of the control group, and no lung metastasis was observed.

Conclusion

Our findings suggest that there is an optimal dose range for the abscopal effect generated with the CIRT combined with anti-CTLA4 antibody, and it highlights a new opportunity for increased induction efficiency of the abscopal effect of combination therapy.

查看原文本刊更多论文

结合碳离子放疗和抗CTLA4抗体诱导脱落效应的最佳放射剂量。

背景与目的：尽管碳离子放疗（CIRT）已取得良好的疗效，但控制转移仍是提高总生存率的关键。本研究旨在评价CIRT与抗ctla4抗体、CIRT与抗pd -1抗体两种组合在不同辐射剂量下对远端肿瘤和转移的抑制效果。材料与方法：将小鼠癌细胞（实验用结肠癌结肠癌-26细胞，验证用骨肉瘤LM8细胞）移植到同基因小鼠后腿两侧。右侧肿瘤用3gy或10gy CIRT照射，左侧肿瘤不照射，随后给予抗ctla4抗体或抗pd -1抗体。照射后，每周测量3次双腿肿瘤直径。放疗后3周内评估肺转移灶数量。结果：与对照组相比，高剂量组在放疗肿瘤和肺转移方面均显示出良好的抗癌效果，但10 Gy CIRT联合抗ctla4抗体或10 Gy CIRT联合抗pd -1抗体均未抑制远端未放疗肿瘤的生长。在低剂量组，对原发肿瘤的控制作用略弱于高剂量治疗组，但在3 Gy CIRT联合抗ctla4抗体治疗后，对远端未照射肿瘤和转移瘤均有显著的抑制作用。具体而言，与对照组相比，远端未照射肿瘤的体积减少了40%，未观察到肺转移。结论：本研究提示CIRT联合抗ctla4抗体产生体外效应存在一个最佳剂量范围，为提高联合治疗体外效应的诱导效率提供了新的机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neoplasia 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

26 days

期刊介绍： Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.