Intralesional targeted alpha therapy for metastatic melanoma
Intralesional targeted alpha therapy for metastatic melanoma
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DOI：
10.4161/cbt.4.12.2251
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发表时间：
2005-12-01
影响因子：
3.6
通讯作者：
Apostolidis, C
中科院分区：
文献类型：
--
作者：
Allen, BJ;Raja, C;Apostolidis, C
本文报道了黑色素瘤病灶内靶向治疗（TAT）的发展和应用，这是建立一种新的全身治疗方案的第一部分。用Bi-213标记良性靶向载体9.2.27，形成α -免疫偶联物（AIC），对靶向黑色素瘤细胞具有高度的细胞毒性。目的：探讨病灶内AIC治疗转移性皮肤黑色素瘤的安全性和有效性。招募了16名黑色素瘤患者。所有患者单克隆抗体均为9.2.27阳性。150 ~ 1350 μ Ci的AIC剂量注射到不同大小的病变中，可以观察到肿瘤碎片的存在，导致大量细胞死亡。AIC在向肿瘤提供高剂量同时保留其他组织方面非常有效。血液蛋白和电解质没有明显变化。没有证据表明存在人抗鼠抗体反应。瘤内TAT治疗黑色素瘤的剂量为1350 μ Ci时相当安全，600 μ Ci时有效。MIA、细胞凋亡和ki67增殖标志物试验均表明TAT是一种很有希望的治疗无法手术的继发性黑色素瘤或原发性眼黑色素瘤的方法。
This paper reports the development and application of intralesional targeted alpha therapy ( TAT) for melanoma, being the first part of a program to establish a new systemic therapy.Rationale. Labelling the benign targeting vector 9.2.27 with Bi-213 forms the alpha-immunoconjugate (AIC), which is highly cytotoxic to targeted melanoma cells.Objective. To investigate the safety and efficacy of intralesional AIC in patients with metastatic skin melanoma.Findings. Sixteen melanoma patients were recruited. All the patients were positive to the monoclonal antibody 9.2.27. AIC doses from 150 to 1350 mu Ci injected into lesions of different sizes resulted in massive cell death, as observed by the presence of tumor debris. The AIC was very effective in delivering a high dose to the tumor while sparing other tissues. There were no significant changes in blood proteins and electrolytes. There was no evidence of a human-antimouse-antibody reaction.Conclusions. Intralesional TAT for melanoma was found to be quite safe up to 1350 mu Ci, and efficacious at a dose of 600 mu Ci. MIA, apoptosis and ki67 proliferation marker tests all indicated that TAT is a promising therapy for the control of inoperable secondary melanoma or primary ocular melanoma.