Regression of metastatic melanoma in a patient by antibody targeting of cancer stem cells

Oncotarget. 2012 Jan;3(1):22-30. doi: 10.18632/oncotarget.437.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies / administration & dosage
  • Antibodies / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Dacarbazine / administration & dosage
  • Foot
  • Humans
  • Male
  • Melanoma / pathology
  • Melanoma / therapy*
  • Molecular Targeted Therapy
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / pathology
  • Remission Induction
  • Rituximab
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Tumor Burden


  • Antibodies
  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab
  • Dacarbazine