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.