Targeting the ITGA3B1 Complex with A Novel Antibody-Drug Conjugate for Metastatic Bladder Cancer
Jung, H.; Lee, J.; Kim, E. G.; Ahn, J.; Haffner, M.; Nelson, P. S.; Kim, K.; Lee, J. K.; Yi, E. C.; Kim, K. M.
Show abstract
Advances in antibody (Ab) phage display technologies have enabled the development of targeted therapies with enhanced precision and clinical efficacy. Here, we report a phenotypic screening strategy combining target-unbiased live-cell biopanning with in situ chemical crosslinking and mass spectrometry to identify internalizing antibodies and their cognate antigens--key features for effective antibody-drug conjugate (ADC) development. Using this approach, we identified the 2E7 antibody, which exhibits rapid internalization and high specificity for the integrin 3{beta}1 (ITGA3B1) heterodimer, a complex overexpressed in multiple solid tumors, including bladder cancer. We generated an ITGA3B1-targeted ADC by conjugating monomethyl auristatin E (MMAE) to the 2E7 antibody, enabling selective delivery of cytotoxic payloads to ITGA3B1-positive cells. In preclinical bladder cancer models, this ADC demonstrated potent and dose-dependent antitumor efficacy, with significant tumor regression and improved survival. Our findings establish a framework for target discovery using live-cell phenotypic screening and position ITGA3B1 as a promising therapeutic target for ADC-based treatment of advanced bladder cancer. TeaserLive-cell biopanning uncovers ITGA3B1 as a target for ADC development in metastatic bladder cancer.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- CYpHER: Catalytic extracellular targeted protein degradation with high potency and durable effect 96%
- Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting 94%
- A Versatile Soluble Siglec Scaffold for Sensitive and Quantitative Detection of Glycan Ligands 94%
Similar papers in this journal
Similar papers in this journal
- Molecular Landscape of Anti-Drug Antibodies Reveals the Mechanism of the Immune Response Following Treatment with TNF-alpha Antagonists 96%
- Opsonization by non-neutralizing antibodies can confer protection to SARS-CoV-2 despite Spike-dependent modulation of phagocytosis 95%
- Harnessing mRNA for the expression of monoclonal IgG and IgA in non-human primates. 95%
Similar papers in this journal
- Piggybacking on the Cholera Toxin: Identification of a Toxoid-binding Protein as an Approach for Targeted Delivery of Proteins to Motor Neurons 93%
- Dual site-specific chemoenzymatic antibody fragment conjugation using CRISPR-based hybridoma engineering 93%
- Modular platform for therapeutic drug delivery using trifunctional bio-orthogonal macromolecular conjugates 92%
Similar papers in this journal
- A self-assembling cross-protective antigen against multiple Gram-positive nosocomial pathogens 94%
- Characterization of the SARS-CoV-2 S Protein: Biophysical, Biochemical, Structural, and Antigenic Analysis 92%
- Nanolipoprotein mediated Her2 protein transfection induces malignant transformation in human breast acinar cultures 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.