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Clinical Trials
Intralesional Targeted Alpha Therapy for Metastatic Melanoma
Barry J Allen, Chand Raja, Syed Rizvi, Yong Li, Wendy Tsui, Peter Graham, John F Thompson, Ralph A. Reisfeld and John Kearsley
volume 4 | issue 12
december 2005Pages: 1318-1324
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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 213Bi 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
16 melanoma patients were recruited. All the patients were positive to the monoclonal antibody 9.2.27. AIC doses from 50 to 450 ?Ci injected into lesions of different sizes resulted in massive cell death, as observed by the presence of tumour debris. The AIC was very effective in delivering a high dose to the tumour while sparing other tissues. There were no significant changes in blood proteins and electrolytes. There was no evidence of a human-antimouse-antibody reaction. Evidence of significant decline in serum marker melanoma-inhibitory-activity protein (MIA) at 2 weeks post-TAT was observed.
Conclusions
Intralesional TAT for melanoma was found to be quite safe up to 450 ?Ci, and efficacious at a dose of 200 ?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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.