Regression of metastatic melanoma by targeting cancer stem cells
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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.
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A pilot study showed median survival exceeding 1 year in patients with metastatic melanoma receiving rituximab.
“A pilot study showed median survival exceeding 1 year in patients with metastatic melanoma receiving RTX.88”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [88]
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- Authors
- Schlaak, M., Schmidt, P., Bangard, C., Kurschat, P., Mauch, C., & Abken, H.
- Affiliations
- University Hospital Cologne (DE)
- University of Cologne (DE)
- Corresponding author
- Schlaak, Max
- Schmidt, Patrick
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2012-01-28
- Volume
- 3
- Issue
- 1
- Pages
- 22-30
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC3292889
- OpenAlex
- W560463957
- Cited by
- 71
- References
- 16
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 10
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsche Krebshilfe
- Universitätsklinikum Köln
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- metastatic melanoma, cancer stem cells, CD20, rituximab, dacarbazine, tumor regression, S-100 protein, serum cytokines, B cell elimination
- MeSH terms
- Rituximab, Aged, Antibodies, Antineoplastic Combined Chemotherapy Protocols, Dacarbazine, Foot, Humans, Male, Melanoma, Remission Induction, Skin Neoplasms, Neoplastic Stem Cells, Tumor Burden, Antibodies, Monoclonal, Murine-Derived, Molecular Targeted Therapy
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