ArticleMolecular cancer therapeutics2022
Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody-drug Conjugate Targeting AXL-expressing Cancers.
Article in Molecular cancer therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 40 citations in OpenAlex.
- Phase I/II Study of AXL-Specific Antibody-Drug Conjugate Enapotamab Vedotin in Patients with Advanced Solid Tumors.Cancer research communications · 2025Trial
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- AXL-directed antibody-drug conjugate therapy in soft-tissue sarcoma.Journal of hematology & oncology · 2026Article
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Sustainable Synthesis and Biological Aspects of Pyrrolobenzodiazepine Derivatives: An Insight Into Current Developments, Structure-Activity Relationships, and Clinical Studies.Chemical record (New York, N.Y.) · 2026Review
- ADC Conjugation Strategies: From Technological Evolution to a Practical Selection Framework.Pharmaceutics · 2026Review
- Site-Specific Glycan Conjugation Improves Stability and Efficacy of an Antibody-Drug Conjugates Bearing DXd as a Cytotoxic Payload.ACS omega · 2026Article
- [Role of Receptor Tyrosine Kinase AXL in Cancer Targeted Therapy Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Glycan Remodeling Technologies for Enhancing Antibody Function.Advances in experimental medicine and biology · 2026Review
- Bispecific Antibody and Antibody-Drug Conjugate as Novel Candidates for Treating Pancreatic Ductal Adenocarcinoma.Biomolecules · 2025Review
- Lineage dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and -independent immunotherapeutic targets.Neuro-oncology · 2025Article
- Opportunities and Challenges in Antibody-Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment.Cancers · 2025Review
- Technical, preclinical, and clinical developments of Fc-glycan-specific antibody-drug conjugates.RSC medicinal chemistry · 2025Review
- Targeting CD19-positive lymphomas with the antibodydrug conjugate loncastuximab tesirine: preclinical evidence of activity as a single agent and in combination therapy.Haematologica · 2024Article
- Hallmarks of pancreatic cancer: spotlight on TAM receptors.EBioMedicine · 2024Review
- Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads.International journal of molecular sciences · 2024Review
- Antibody-Drug Conjugates-Evolution and Perspectives.International journal of molecular sciences · 2024Review
- Chemical immunology: Recent advances in tool development and applications.Cell chemical biology · 2024Review
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AXL, a tyrosine kinase receptor that is overexpressed in many solid and hematologic malignancies, facilitates cancer progression and is associated with poor clinical outcomes. Importantly, drug-induced expression of AXL results in resistance to conventional chemotherapy and targeted therapies. Together with its presence on multiple cell types in the tumor immune microenvironment, these features make it an attractive therapeutic target for AXL-expressing malignancies. ADCT-601 (mipasetamab uzoptirine) is an AXL-targeted antibody-drug conjugate (ADC) comprising a humanized anti-AXL antibody site specifically conjugated using GlycoConnect technology to PL1601, which contains HydraSpace, a Val-Ala cleavable linker and the potent pyrrolobenzodiazepine (PBD) dimer cytotoxin SG3199. This study aimed to validate the ADCT-601 mode of action and evaluate its efficacy in vitro and in vivo, as well as its tolerability and pharmacokinetics. ADCT-601 bound to both soluble and membranous AXL, and was rapidly internalized by AXL-expressing tumor cells, allowing release of PBD dimer, DNA interstrand cross-linking, and subsequent cell killing. In vivo, ADCT-601 had potent and durable antitumor activity in a wide variety of human cancer xenograft mouse models, including patient-derived xenograft models with heterogeneous AXL expression where ADCT-601 antitumor activity was markedly superior to an auristatin-based comparator ADC. Notably, ADCT-601 had antitumor activity in a monomethyl auristatin E-resistant lung-cancer model and synergized with the PARP inhibitor olaparib in a BRCA1-mutated ovarian cancer model. ADCT-601 was well tolerated at doses of up to 6 mg/kg and showed excellent stability in vivo. These preclinical results warrant further evaluation of ADCT-601 in the clinic.
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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.