Regression of metastatic melanoma by targeting cancer stem cells

Current therapeutic regimens attempt to eliminate all malignant cells of a melanoma lesion. Pre-clinical data, however, indicate that melanoma is maintained by a minor subset of cancer cells, which are characterized by CD20 expression. We attempted to eliminate those cells in a progressing, chemotherapy-refractory metastatic melanoma patient by lesional injections of the anti-CD20 therapeutic antibody rituximab and concomitant dacarbazine treatment, which was ineffective as monotherapy. Although the frequency of CD20(+) melanoma cells within the tumor lesions was initially about 2% and the bulk of tumor cells did not express CD20, rituximab treatment produced lasting remission accompanied by a decline of the melanoma serum marker S-100 to physiological levels. Detailed in-depth-analyses revealed a switch of serum cytokines from a T helper-2 to a pro-inflammatory T helper-1 cell profile. Apart from B cell elimination and decline in gammaglobulin levels, no grade 3/4 toxicity related to treatment was observed. Data provide the first clinical evidence that targeting the minor subset of CD20(+) “melanoma sustaining cells” produces regression of chemotherapy-refractory melanoma and highlight the potency of selective cancer cell targeting in the treatment of melanoma.