Intralesional targeted alpha therapy for metastatic melanoma

Abstract

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 alphaimmunoconjugate (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 μCi 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. Evidence of significant decline in serum marker melanoma-inhibitory-activity protein (MIA) at two weeks post-TAT was observed. Conclusions. Intralesional TAT for melanoma was found to be quite safe up to 1350 μCi, and efficacious at a dose of 600 μCi. 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. ©2005 Landes Bioscience.