ArticleMolecular therapy oncolytics2021
Preclinical evaluation of a novel antibody-drug conjugate targeting DR5 for lymphoblastic leukemia therapy.
Article in Molecular therapy oncolytics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies.Drug delivery · 2026Review
- Delivery of Monomethyl Auristatin E Using Ionizable Lipid Nanoparticles for B‑Cell Acute Lymphoblastic Leukemia Treatment.ACS omega · 2026Article
- Antibody-drug conjugates in colorectal cancer: advances in targeted delivery and personalized oncology.Frontiers in bioengineering and biotechnology · 2026Review
- Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer.Cell reports. Medicine · 2025Article
- A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Combined therapy of dabrafenib and an anti-HER2 antibody-drug conjugate for advanced BRAF-mutant melanoma.Cellular & molecular biology letters · 2024Article
- Therapeutic efficacy of a MMAE-based anti-DR5 drug conjugate Oba01 in preclinical models of pancreatic cancer.Cell death & disease · 2023Article
- An Enzymatically Cleavable Tripeptide Linker for Maximizing the Therapeutic Index of Antibody-Drug Conjugates.Molecular cancer therapeutics · 2022Article
- Subcellular Proteome Analysis Reveals Apoptotic Vulnerability of T-Cell Acute Lymphoblastic Leukemia.BioMed research international · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute lymphoblastic leukemia (ALL) is an aggressive hematological neoplasm resulting from immature lymphoid precursors. An antibody-drug conjugate (ADC), coupling a small molecule covalently with a targeting antibody, can specifically kill tumor cells. Death receptor 5 (DR5) is considered as a promising anti-tumor drug target. In this study, we describe the preclinical evaluation of a novel DR5-targeting ADC (Oba01) as a potential therapeutic against ALL. Oba01 utilizes anti-DR5 humanized monoclonal antibody (zaptuzumab) coupled via a cleavable linker to monomethyl auristatin E (MMAE). Oba01 can specifically bind to DR5 on the tumor cells and transfer into lysosome via DR5-mediated endocytosis. It then effectively releases the MMAE, which can bind to the tubulin and prevent its aggregation, thereby leading to a significant inhibition of proliferation and cell death in tumor cells. Additionally, Oba01 displays significant dose-dependent tumoricidal activity in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. More importantly, toxicity analysis of Oba01 showed a favorable safety profile, and pharmacokinetic analysis illustrated an excellent stability and tolerability in rats and cynomolgus monkeys. Taken together, our data conclusively demonstrate that Oba01 is an attractive candidate for further clinical trials in DR5-positive ALL patients.
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