ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
A highly stable human single-domain antibody-drug conjugate exhibits superior penetration and treatment of solid tumors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 70 citations in OpenAlex.
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- Tiny tools closing the gap: nanobodies in research and therapy.Function (Oxford, England) · 2026Review
- GD2-Targeted Minibody-Drug Conjugates Match the Potency of IgG-Based ADCs in a Mouse Cancer Model.International journal of molecular sciences · 2026Article
- NIR Ratiometric Fluorescent Antibody-Drug Conjugate for Metastatic Ovarian Cancer Theranostics and Treatment Response Monitoring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Novel anti-HER2 nanobody-drug conjugates with enhanced penetration of solid tumor and BBB, reduced systemic exposure and superior antitumor efficacy.Acta pharmacologica Sinica · 2026Article
- An Engineered Probiotic Consortium Based on Quorum-Sensing for Colorectal Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Noncanonical amino acid-aided synthesis of anti-PD-L1 bispecific nanobody for colon cancer immunotherapy.Communications biology · 2025Article
- Chemotherapeutic Drug-Antibody Conjugates (ChemoBodies): Recent Advances and Future Directions.Current oncology reports · 2025Review
- A synergistic generative-ranking framework for tailored design of therapeutic single-domain antibodies.Cell discovery · 2025Article
- Development of a novel anti-CEACAM5 VHH for SPECT imaging and potential cancer therapy applications.European journal of nuclear medicine and molecular imaging · 2025Article
- Engineering a novel light-chain single-domain antibody to enable IgG-format bispecific antibody design.Antibody therapeutics · 2025Article
- Topical delivery of a human single-domain antibody targeting IL-33 to inhibit mucosal inflammation.Cellular & molecular immunology · 2025Article
- The Icarian flight of antibody-drug conjugates: target selection amidst complexity and tackling adverse impacts.Protein & cell · 2025Review
- Nanobodies: From Discovery to AI-Driven Design.Biology · 2025Review
- Synergistic approach to combating triple-negative breast cancer: DDR1-targeted antibody-drug conjugate combined with pembrolizumab.Journal of pharmaceutical analysis · 2025Article
- Trends in nanobody radiotheranostics.European journal of nuclear medicine and molecular imaging · 2025Review
- Development of Fully Human Antibodies Targeting SIRPα and PLA2G7 for Cancer Therapy.Antibodies (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inefficient tumor penetration of therapeutic antibodies has hampered their effective use in treating solid tumors. Here, we report the identification of a fully human single-domain antibody (UdAb), designated as n501, targeting the oncofetal antigen 5T4. The high-resolution crystal structure indicates that n501 adopts a compact structure very similar to that of camelid nanobodies, and binds tightly to all eight leucine-rich repeats of 5T4. Furthermore, the UdAb n501 exhibits exceptionally high stability, with no apparent activity changes over 4 weeks of storage at various temperatures. Importantly, the UdAb-based antibody-drug conjugate (n501-SN38) showed much deeper tumor penetration, significantly higher tumor uptake, and faster accumulation at tumor sites than conventional IgG1-based antibody-drug conjugate (m603-SN38), resulting in improved tumor inhibition. These results highlight the potential of UdAb-based antibody-drug conjugates as a potential class of antitumor therapeutics with characteristics of high stability and strong tumor penetration for the effective treatment of solid tumors.
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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.