Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Biomed Pharmacother. 2023 Apr;160:114390. doi: 10.1016/j.biopha.2023.114390. Epub 2023 Feb 13.
The bones are a common site for metastasis arising from solid tumors such as breast and prostate cancer. Chemotherapy, including immunotherapy, is rarely curative. Radiotherapy with pain palliation can temporize bone metastases but is generally considered a short-term solution and retreatment is difficult. Surgery is often necessary, yet recovery times might exceed life expectancy. Therefore, there is a need to develop new approaches to bone metastases that are effective but minimally invasive. Near-infrared photoimmunotherapy (NIR-PIT) uses antibodies labeled with IRDye700DX (IR700) which is activated by NIR light, resulting in rapid cell membrane damage and immunogenic cell death. NIR-PIT using an anti-epidermal growth factor receptor (EGFR) antibody-IR700 conjugate in patients with recurrent head and neck cancer received qualified approval in Japan in 2020 and is now widely used there. However, no bone metastases have yet been treated. In this study, the efficacy of NIR-PIT for bone metastases was investigated using a bone metastases mouse model successfully established by caudal artery injection of a human triple-negative breast cancer cell line, MDAMB468-GFP/luc. The bone metastatic lesions were treated with NIR-PIT using the anti-EGFR antibody, panitumumab-IR700 conjugate. Bioluminescence imaging and histological evaluation showed that EGFR-targeted NIR-PIT has a therapeutic effect on bone metastatic lesions in mice. In addition, micro-CT showed that repeated NIR-PIT led to repair of metastasis-induced bone destruction and restored bone cortex continuity consistent with healing. These data suggest that NIR-PIT has the potential for clinical application in the treatment of bone metastases.
骨骼是乳腺癌和前列腺癌等实体瘤转移的常见部位。化疗,包括免疫疗法,很少能根治。放射治疗可缓解疼痛,但只能暂时缓解骨转移,通常被认为是一种短期解决方案,且再次治疗较为困难。手术通常是必要的,但恢复时间可能超过预期寿命。因此,需要开发新的方法来治疗骨转移,这些方法既要有效又要微创。近红外光免疫治疗(NIR-PIT)使用标记有 IRDye700DX(IR700)的抗体,IR700 可被近红外光激活,导致快速的细胞膜损伤和免疫原性细胞死亡。2020 年,日本批准了使用针对表皮生长因子受体(EGFR)的抗体-IR700 缀合物对复发性头颈部癌症患者进行 NIR-PIT 的合格批准,目前已在日本广泛使用。但是,尚未治疗骨转移。在这项研究中,通过尾动脉注射人三阴性乳腺癌细胞系 MDAMB468-GFP/luc 成功建立了骨转移小鼠模型,研究了 NIR-PIT 对骨转移的疗效。使用抗 EGFR 抗体,panitumumab-IR700 缀合物对骨转移病灶进行 NIR-PIT 治疗。生物发光成像和组织学评估表明,针对 EGFR 的 NIR-PIT 对小鼠骨转移病灶具有治疗作用。此外,Micro-CT 显示,重复 NIR-PIT 可修复转移引起的骨破坏,并恢复与愈合一致的骨皮质连续性。这些数据表明,NIR-PIT 有可能应用于骨转移的临床治疗。
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