ArticleCancers2020
A Novel Antibody-Drug Conjugate (ADC) Delivering a DNA Mono-Alkylating Payload to Chondroitin Sulfate Proteoglycan (CSPG4)-Expressing Melanoma.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Therapeutic Resistance in Melanoma: Molecular Mechanisms and Emerging Pharmaceutical Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- An antibody-drug conjugate designed through clone and isotype selection restricts the growth of CSPG4-expressing triple-negative breast cancer.NPJ precision oncology · 2026Article
- Proteoglycans in Breast Cancer: Friends and Foes.Biomolecules · 2025Review
- Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer.Cancers · 2025Review
- Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma.Cancers · 2024Review
- Antibody-Drug Conjugates in the Pipeline for Treatment of Melanoma: Target and Pharmacokinetic Considerations.Drugs in R&D · 2024Review
- Trends in the Development of Antibody-Drug Conjugates for Cancer Therapy.Antibodies (Basel, Switzerland) · 2023Review
- CSPG4 as a target for the specific killing of triple-negative breast cancer cells by a recombinant SNAP-tag-based antibody-auristatin F drug conjugate.Journal of cancer research and clinical oncology · 2023Article
- Immunohistochemical detection of the chondroitin sulfate proteoglycan 4 protein in primary and metastatic melanoma.Oncology letters · 2023Article
- Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4.Nature communications · 2023Article
- Mechanistic insight into the repair of C8-linked pyrrolobenzodiazepine monomer-mediated DNA damage.RSC medicinal chemistry · 2022Article
- CSPG4 expression in soft tissue sarcomas is associated with poor prognosis and low cytotoxic immune response.Journal of translational medicine · 2022Article
- The Potential of Antibody Technology and Silver Nanoparticles for Enhancing Photodynamic Therapy for Melanoma.Biomedicines · 2022Review
- Emerging drug targets for triple-negative breast cancer: a guided tour of the preclinical landscape.Expert opinion on therapeutic targets · 2022Review
- CSPG4 Expression in GIST Is Associated with Better Prognosis and Strong Cytotoxic Immune Response.Cancers · 2022Article
- A Comparative View on Molecular Alterations and Potential Therapeutic Strategies for Canine Oral Melanoma.Veterinary sciences · 2021Review
- Immunotherapy using IgE or CAR T cells for cancers expressing the tumor antigen SLC3A2.Journal for immunotherapy of cancer · 2021Article
- Expression of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma cells is downregulated upon inhibition of BRAF.Oncology reports · 2021Article
- Article
- Antibody-Based Immunotherapy: Alternative Approaches for the Treatment of Metastatic Melanoma.Biomedicines · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Despite emerging targeted and immunotherapy treatments, no monoclonal antibodies or antibody-drug conjugates (ADCs) directly targeting tumor cells are currently approved for melanoma therapy. The tumor-associated antigen chondroitin sulphate proteoglycan 4 (CSPG4), a neural crest glycoprotein over-expressed on 70% of melanomas, contributes to proliferative signaling pathways, but despite highly tumor-selective expression it has not yet been targeted using ADCs. We developed a novel ADC comprising an anti-CSPG4 antibody linked to a DNA minor groove-binding agent belonging to the novel pyrridinobenzodiazepine (PDD) class. Unlike conventional DNA-interactive pyrrolobenzodiazepine (PBD) dimer payloads that cross-link DNA, PDD-based payloads are mono-alkylating agents but have similar efficacy and substantially enhanced tolerability profiles compared to PBD-based cross-linkers. We investigated the anti-tumor activity and safety of the anti-CSPG4-(PDD) ADC in vitro and in human melanoma xenografts. Anti-CSPG4-(PDD) inhibited CSPG4-expressing melanoma cell growth and colony formation and triggered apoptosis in vitro at low nanomolar to picomolar concentrations without off-target Fab-mediated or Fc-mediated toxicity. Anti-CSPG4-(PDD) restricted xenograft growth in vivo at 2 mg/kg doses. One 5 mg/kg injection triggered tumor regression in the absence of overt toxic effects or of acquired residual tumor cell resistance. This anti-CSPG4-(PDD) can deliver a highly cytotoxic DNA mono-alkylating payload to CSPG4-expressing tumors at doses tolerated in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.