ArticleProceedings of the National Academy of Sciences of the United States of America2013
Bispecific small molecule-antibody conjugate targeting prostate cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04077021 (A Phase 1, Open-label Study in Two Parts, Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of CCW702 in Patients With Metastatic, Castration Resistant Prostate Adenocarcinoma), which is not on this map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Phase 1, Open-label Study in Two Parts, Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of CCW702 in Patients With Metastatic, Castration Resistant Prostate Adenocarcinoma
Who cites it
48 citing papers in PubMed, 84 citations in OpenAlex.
- Site-Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids.Angewandte Chemie (International ed. in English) · 2026Review
- Synthesis of Bispecific Conjugates by ADP-Ribosyl Cyclases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Development and Optimization of an Aminooxy Coupling Reaction to Prepare Multivalent Bioconjugates with a Single Noncanonical Amino Acid.Bioconjugate chemistry · 2026Article
- Bispecific antibodies in metastatic castration-resistant prostate cancer: therapeutic strategies and frontier advances.World journal of urology · 2025Review
- Synthesis of site-specific Fab-drug conjugates using ADP-ribosyl cyclases.Protein science : a publication of the Protein Society · 2024Article
- Systematic Evaluation of Protein-Small Molecule Hybrids on the Yeast Surface.ACS chemical biology · 2024Article
- Introduction of Carbonyl Groups into Antibodies.Molecules (Basel, Switzerland) · 2023Review
- Site-Specific Antibody Conjugation with Payloads beyond Cytotoxins.Molecules (Basel, Switzerland) · 2023Review
- Protein Modification Employing Non-Canonical Amino Acids to Prepare SUMOylation Detecting Bioconjugates.Pharmaceutics · 2022Article
- Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.World journal of urology · 2022Article
- An efficient cell-free protein synthesis platform for producing proteins with pyrrolysine-based noncanonical amino acids.Biotechnology journal · 2022Article
- Making Sense of "Nonsense" and More: Challenges and Opportunities in the Genetic Code Expansion, in the World of tRNA Modifications.International journal of molecular sciences · 2022Review
- A PSMA-targeted bispecific antibody for prostate cancer driven by a small-molecule targeting ligand.Science advances · 2021Article
- Strategies for targeting cell surface proteins using multivalent conjugates and chemical biology.Methods in cell biology · 2021Article
- Rapid Evaluation of Antibody Fragment Endocytosis for Antibody Fragment-Drug Conjugates.Biomolecules · 2020Article
- Revisiting Immunotherapy: A Focus on Prostate Cancer.Cancer research · 2020Review
- Site-specific antibody fragment conjugates for targeted imaging.Methods in enzymology · 2020Article
- Tumor Uptake of Triazine Dendrimers Decorated with Four, Sixteen, and Sixty-Four PSMA-Targeted Ligands: Passive versus Active Tumor Targeting.Biomolecules · 2019Article
- Site-Specific Immuno-PET Tracer to Image PD-L1.Molecular pharmaceutics · 2019Article
- Design, synthesis and evaluation of anti-CD38 antibody drug conjugate based on Daratumumab and maytansinoid.Bioorganic & medicinal chemistry · 2019Article
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.
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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.