ArticleMolecular cancer2010
Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP)-targeted delivery of soluble TRAIL potently inhibits melanoma outgrowth in vitro and in vivo.
Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 72 citations in OpenAlex.
- Review
- Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer.Cancers · 2025Review
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- Beyond ADCs: harnessing bispecific antibodies to directly induce apoptosis for targeted tumor eradication.Antibody therapeutics · 2024Review
- Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma.Cancers · 2024Review
- Secretome profiling reveals acute changes in oxidative stress, brain homeostasis, and coagulation following short-duration spaceflight.Nature communications · 2024Article
- Chondroitin sulfate proteoglycan 4: An attractive target for antibody-based immunotherapy.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2024Review
- Immunohistochemical detection of the chondroitin sulfate proteoglycan 4 protein in primary and metastatic melanoma.Oncology letters · 2023Article
- Application of an Autoinduction Strategy to Optimize the Heterologous Production of an Antitumor Bispecific Fusion Protein Based on the TRAIL Receptor-Selective Mutant Variant in Escherichia coli.Molecular biotechnology · 2023Article
- Extracellular vesicles from hair follicle-derived mesenchymal stromal cells: isolation, characterization and therapeutic potential for chronic wound healing.Stem cell research & therapy · 2022Article
- A chondroitin sulfate proteoglycan 4‑specific monoclonal antibody inhibits melanoma cell invasion in a spheroid model.International journal of oncology · 2021Article
- In Like a Lamb; Out Like a Lion: Marching CAR T Cells Toward Enhanced Efficacy in B-ALL.Molecular cancer therapeutics · 2021Review
- Review
- Evaluating the Combination of Radioimmunotherapy and Immunotherapy in a Melanoma Mouse Model.International journal of molecular sciences · 2020Article
- Article
- Article
- Molecular Mode of Action of TRAIL Receptor Agonists-Common Principles and Their Translational Exploitation.Cancers · 2019Review
- CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia.International journal of molecular sciences · 2019Article
- Immunomagnetic-Enriched Subpopulations of Melanoma Circulating Tumour Cells (CTCs) Exhibit Distinct Transcriptome Profiles.Cancers · 2019Article
- Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells.Journal of cancer research and clinical oncology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdvanced melanoma is characterized by a pronounced resistance to therapy leading to a limited patient survival of ~6 - 9 months. Here, we report on a novel bifunctional therapeutic fusion protein, designated anti-MCSP:TRAIL, that is comprised of a melanoma-associated chondroitin sulfate proteoglycan (MCSP)-specific antibody fragment (scFv) fused to soluble human TRAIL. MCSP is a well-established target for melanoma immunotherapy and has recently been shown to provide important tumorigenic signals to melanoma cells. TRAIL is a highly promising tumoricidal cytokine with no or minimal toxicity towards normal cells. Anti-MCSP:TRAIL was designed to 1. selectively accrete at the cell surface of MCSP-positive melanoma cells and inhibit MCSP tumorigenic signaling and 2. activate apoptotic TRAIL-signaling.
resultsTreatment of a panel of MCSP-positive melanoma cell lines with anti-MCSP:TRAIL induced TRAIL-mediated apoptotic cell death within 16 h. Of note, treatment with anti-MCSP:sTRAIL was also characterized by a rapid dephosphorylation of key proteins, such as FAK, implicated in MCSP-mediated malignant behavior. Importantly, anti-MCSP:TRAIL treatment already inhibited anchorage-independent growth by 50% at low picomolar concentrations, whereas > 100 fold higher concentrations of non-targeted TRAIL failed to reduce colony formation. Daily i.v. treatment with a low dose of anti-MCSP:TRAIL (0.14 mg/kg) resulted in a significant growth retardation of established A375 M xenografts. Anti-MCSP:TRAIL activity was further synergized by co-treatment with rimcazole, a σ-ligand currently in clinical trials for the treatment of various cancers.
conclusionsAnti-MCSP:TRAIL has promising pre-clinical anti-melanoma activity that appears to result from combined inhibition of tumorigenic MCSP-signaling and concordant activation of TRAIL-apoptotic signaling. Anti-MCSP:TRAIL alone, or in combination with rimcazole, may be of potential value for the treatment of malignant melanoma.
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