title: Regression of metastatic melanoma in a patient by antibody targeting of cancer stem cells.
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.
authors.affiliation: Department of Dermatology and Venerology, Skin Cancer Center at the Center for Integrated Oncology, University of Cologne, Cologne, Germany
authors.forename: Max
authors.initials: M
authors.lastname: Schlaak
authors.forename: Patrick
authors.initials: P
authors.lastname: Schmidt
authors.forename: Christopher
authors.initials: C
authors.lastname: Bangard
authors.forename: Peter
authors.initials: P
authors.lastname: Kurschat
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
mesh_terms: D000368:Aged; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003606:Dacarbazine / Q000008:administration & dosage; D005528:Foot; D006801:Humans; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D012074:Remission Induction; D000069283:Rituximab; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D047368:Tumor Burden
chemical_list: D000906:Antibodies; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D003606:Dacarbazine