Oncotarget

Brief Reports:

Regression of metastatic melanoma by targeting cancer stem cells

Max Schlaak, Patrick Schmidt, Christopher Bangard, Peter Kurschat, Cornelia Mauch and Hinrich Abken _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2012; 3:22-30. https://doi.org/10.18632/oncotarget.437

Metrics: PDF 2314 views  |   HTML 2740 views  |   ?  


Abstract

Max Schlaak1,*, Patrick Schmidt2,*,+, Christopher Bangard3, Peter Kurschat1, Cornelia Mauch1,4, and Hinrich Abken2,4

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 437