Dead cells in melanoma tumors provide abundant antigen for targeted delivery of ionizing radiation by a mAb to melanin.

Abstract

Melanoma is a cancer with a rising incidence, and metastatic disease is almost always lethal. We investigated the feasibility of targeting melanin, an intracellular melanocyte pigment, to deliver cytotoxic radiation to human melanoma cells in vivo by using a melanin-binding mAb (6D2). Nude mice bearing MNT1 pigmented human melanoma tumors were treated with mAb 6D2 labeled with 1.5 mCi (1 Ci = 37 GBq) of the beta-emitter 188-Rhenium (188Re) and manifested inhibition of tumor growth and prolonged survival. mAb 6D2 bound tumor melanin and demonstrated no crossreactivity with normal melanized tissues in black mice. The mechanism of melanin targeting involved Ab binding to extracellular melanin released during tumor cell turnover or to dying cells with permeable membranes. In this approach, the cytotoxic radiation emanating from labeled Ab bound to melanin is presumably delivered by "crossfire" effect to the adjacent viable tumor cells. Our results establish the feasibility of targeting melanin released from dead melanoma cells in tumors with radiolabeled Abs to achieve a therapeutic effect. In contrast to conventional tumor antigens, melanin is insoluble, resistant to degradation, and can be expected to accumulate in targeted tissues, suggesting that the efficacy of therapy could increase with each subsequent treatment cycle.

• Authors: Ekaterina Dadachova, Joshua D Nosanchuk, Li Shi, Andrew D Schweitzer, Annie Frenkel, Jerome S Nosanchuk, Arturo Casadevall
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 41 Pg. 14865-70 (Oct 12 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15469923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antigens, Neoplasm
• Melanins

Topics

• Animals
• Antibodies, Monoclonal
• Antigens, Neoplasm (immunology)
• Cell Death
• Cell Line, Tumor
• Dose-Response Relationship, Radiation
• Humans
• Melanins (immunology)
• Melanoma (pathology, radiotherapy)
• Mice
• Mice, Nude
• Radiation, Ionizing
• Radioimmunotherapy (methods)
• Transplantation, Heterologous