Renaissance of targeting molecules for melanoma.

Malignant melanoma affects approximately 40,000 new patients each year in the United States and an estimated 100,000 people worldwide. There is no satisfactory treatment for patients with metastatic melanoma that have an estimated 5-year survival of 6%. The potential of radioimmunotherapy (RIT) for the treatment of metastatic melanoma was recognized very early by RIT pioneers when murine melanoma was successfully treated by DeNardo, and later when Larson reported a shrinkage of tumor in a patient with metastatic melanoma treated with 131I-labeled Fab' fragments of a mAb against high-molecular-weight melanoma-associated antigen. Despite successes in the 1980s, RIT of melanoma did not develop into a clinical modality. The reasons for this are complex. In recent years, RIT has made an impression, as evidenced by the recent approval of Zevalin and Bexxar (anti-CD20 mAbs labeled with 90Y and 131I, respectively). Now there is a "window of opportunity" for RIT to become an effective therapy for metastatic melanoma. Surface antigen GD3 has been evaluated in patients as a potential target for melanoma RIT; pretargeting the administration of antibodies and intralesional administration of an antibody labeled with potent alpha-emitter 213-Bismuth have shown promise in clinical studies. Melanin, the pigment that gives melanoma its name, has emerged as a novel antigen for delivery of radioactivity to the tumors by antimelanin antibody. Simultaneously, radiolabeled metal-cyclized alpha-MSH peptide analogs and melanin-binding peptides are being developed as targeting molecules for melanoma. Overall, we are hopeful that targeted radionuclide therapy of metastatic melanoma will become a reality within the next few years.