ArticleJournal for immunotherapy of cancer2022
Therapeutic efficacy of antibody-drug conjugates targeting GD2-positive tumors.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- GD2-Targeted Minibody-Drug Conjugates Match the Potency of IgG-Based ADCs in a Mouse Cancer Model.International journal of molecular sciences · 2026Article
- Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies.Oncology research · 2026Review
- Ganglioside therapy in cancer molecular insights and therapeutic opportunities.Discover oncology · 2025Review
- Antibody drug conjugates in metastatic brain tumors: current landscape, therapeutic potential and challenges.Journal of neuro-oncology · 2025Review
- SC134-deruxtecan, a fucosyl-GM1 targeting ADC for small cell lung cancer therapy.Journal of translational medicine · 2025Article
- Tumor glyco-immunology, glyco-immune checkpoints and immunotherapy.Journal for immunotherapy of cancer · 2025Review
- Transcriptome-Wide Analysis of Pituitary and Ectopic Adrenocorticotropic Hormone-Secreting Tumors.Cancers · 2025Article
- Assessment of targets of antibody drug conjugates in SCLC.NPJ precision oncology · 2025Article
- Antibody conjugates in neuroblastoma: a step forward in precision medicine.Frontiers in oncology · 2025Review
- Ganglioside GD2 Contributes to a Stem-Like Phenotype in Intrahepatic Cholangiocarcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Antibody-drug conjugates in cancer therapy: innovations, challenges, and future directions.Archives of pharmacal research · 2024Review
- The Evolving Landscape of Antibody-Drug Conjugates: In Depth Analysis of Recent Research Progress.Bioconjugate chemistry · 2023Review
- The Ying and Yang of Ganglioside Function in Cancer.Cancers · 2023Review
- Targeting GD2-Positive Tumor Cells by Pegylated scFv Fragment-Drug Conjugates Carrying Maytansinoids DM1 and DM4.Current issues in molecular biology · 2023Article
- Antitumor activity of the investigational B7-H3 antibody-drug conjugate, vobramitamab duocarmazine, in preclinical models of neuroblastoma.Journal for immunotherapy of cancer · 2023Article
- Article
- Review
- Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities.Archives of pharmacal research · 2023Review
- Aminooxy Click Modification of a Periodate-Oxidized Immunoglobulin G: A General Approach to Antibody-Drug Conjugates with Dye-Mediated Expeditious Stoichiometry Control.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBoth ganglioside GD2-targeted immunotherapy and antibody-drug conjugates (ADCs) have demonstrated clinical success as solid tumor therapies in recent years, yet no research has been carried out to develop anti-GD2 ADCs against solid tumors. This is the first study to analyze cytotoxic activity of clinically relevant anti-GD2 ADCs in a wide panel of cell lines with varying GD2 expression and their effects in mouse models of GD2-positive solid cancer.
methodsAnti-GD2 ADCs were generated based on the GD2-specific antibody ch14.18 approved for the treatment of neuroblastoma and commonly used drugs monomethyl auristatin E (MMAE) or F (MMAF), conjugated via a cleavable linker by thiol-maleimide chemistry. The antibody was produced in a mammalian expression system, and its specific binding to GD2 was analyzed. Antigen-binding properties and biodistribution of the ADCs in mice were studied in comparison with the parent antibody. Cytotoxic effects of the ADCs were evaluated in a wide panel of GD2-positive and GD2-negative tumor cell lines of neuroblastoma, glioma, sarcoma, melanoma, and breast cancer. Their antitumor effects were studied in the B78-D14 melanoma and EL-4 lymphoma syngeneic mouse models.
resultsThe ch14.18-MMAE and ch14.18-MMAF ADCs retained antigen-binding properties of the parent antibody. Direct dependence of the cytotoxic effect on the level of GD2 expression was observed in cell lines of different origin for both ADCs, with IC50 below 1 nM for the cells with high GD2 expression and no cytotoxic effect for GD2-negative cells. Within the analyzed cell lines, ch14.18-MMAF was more effective in the cells overexpressing GD2, while ch14.18-MMAE had more prominent activity in the cells expressing low GD2 levels. The ADCs had a similar biodistribution profile in the B78-D14 melanoma model compared with the parent antibody, reaching 7.7% ID/g in the tumor at 48 hours postinjection. The average tumor size in groups treated with ch14.18-MMAE or ch14.18-MMAF was 2.6 times and 3.8 times smaller, respectively, compared with the control group. Antitumor effects of the anti-GD2 ADCs were also confirmed in the EL-4 lymphoma model.
conclusionThese findings validate the potential of ADCs targeting ganglioside GD2 in treating multiple GD2-expressing solid tumors.
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