ArticleBiomolecules2020
Site-Specific Antibody-Drug Conjugates in Triple Variable Domain Fab Format.
Article in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Strategic and Chemical Advances in Antibody-Drug Conjugates.Pharmaceutics · 2025Review
- Targeting prostate cancer with site-specific antibody-drug conjugates enabled by tandemly fused ADP-ribosyl cyclases.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- A review of conjugation technologies for antibody drug conjugates.Antibody therapeutics · 2025Review
- A humanized trivalent Nectin-4-targeting nanobody drug conjugate displays potent antitumor activity in gastric cancer.Journal of nanobiotechnology · 2024Article
- Synthesis of site-specific Fab-drug conjugates using ADP-ribosyl cyclases.Protein science : a publication of the Protein Society · 2024Article
- Leveraging a Dual Variable Domain Immunoglobulin to Create a Site-Specifically Modified Radioimmunoconjugate.Molecular pharmaceutics · 2023Article
- Sculpting a Uniquely Reactive Cysteine Residue for Site-Specific Antibody Conjugation.Bioconjugate chemistry · 2022Article
- Recent developments in chemical conjugation strategies targeting native amino acids in proteins and their applications in antibody-drug conjugates.Chemical science · 2021Review
- Site-selective lysine conjugation methods and applications towards antibody-drug conjugates.Chemical communications (Cambridge, England) · 2021Review
- Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress.Journal of hematology & oncology · 2021Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The interest in replacing the conventional immunoglobulin G (IgG) format of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) with alternative antibody and antibody-like scaffolds reflects a need to expand their therapeutic utility and potency while retaining their exquisite specificity, affinity, and low intrinsic toxicity. For example, in the therapy of solid malignancies, the limited tumor tissue penetration and distribution of ADCs in IgG format mitigates a uniform distribution of the cytotoxic payload. Here, we report triple variable domain Fab (TVD-Fab) as a new format that affords the site-specific and stable generation of monovalent ADCs without the Fc domain and a drug-to-antibody ratio (DAR) of 2. TVD-Fabs harbor three variable fragment (Fv) domains: one for tumor targeting and two for the fast, efficient, precise, and stable conjugation of two cargos via uniquely reactive lysine residues. The biochemical and in vitro cytotoxicity properties of a HER2-targeting TVD-Fab before and after conjugation to a tubulin inhibitor were validated. In vivo, the TVD-Fab antibody carrier revealed a circulatory half-life of 13.3 ± 2.5 h and deeper tumor tissue distribution compared to our previously reported dual variable domain (DVD)-IgG1 format. Taken together, the TVD-Fab format merits further investigations as an antibody carrier of site-specific ADCs targeting solid malignancies.
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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.