Regression of metastatic melanoma by targeting cancer stem cells

Max Schlaak 1,* , Patrick Schmidt 2,*,+ , Christopher Bangard 3 , Peter Kurschat 1 , Cornelia Mauch 1,4 , and Hinrich Abken 2,4 1 Department of Dermatology and Venerology, Skin Cancer Center at the Center for Integrated Oncology 2 Tumorgenetics, Department I of Internal Medicine 3 Institute for Radiological Diagnostics 4 Center for Molecular Medicine Cologne, University of Cologne, D-50931 Cologne, Germany + Present Address: Cancer Stem Cell Laboratory, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland * Denotes equal contribution Received: January 21, 2012; Accepted: January 25, 2012; Published: January 28, 2012; Keywords: cancer stem cell, melanoma, CD20, rituximab Correspondence: Hinrich Abken, email: // // Abstract Current therapeutic regimens attempt to eliminate all malignant cells of a melanoma lesion; pre-clinical data, however, indicate that melanoma, once established, is maintained by a minor, non-random subset of cancer cells which are characterized by CD20 expression. We asked to eliminate those cells in a progressing, chemotherapy-refractory metastatic melanoma patient by lesional injections of the anti-CD20 therapeutic antibody rituximab and concomitant low dose systemic dacarbazine treatment. Although the frequencies of CD20 + melanoma cells within the tumor lesions were initially about 2% and the bulk of tumor cells did not express CD20, rituximab treatment produced lasting remission of treated tumor lesions in the long-term. Remission was 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.