ArticlemAbs2014
A general strategy for generating intact, full-length IgG antibodies that penetrate into the cytosol of living cells.
Article in mAbs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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The trial behind it
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Cytoplasmic delivery of antibodies through grafting a functional single complementarity-determining region loop.FEBS letters · 2025Article
- Tumor-specific cytosol-penetrating antibodies for antigen- and TME-dependent intracellular cargo delivery.Molecular therapy. Oncology · 2025Article
- A Conditionally Activated Cytosol-Penetrating Antibody for TME-Dependent Intracellular Cargo Delivery.Antibodies (Basel, Switzerland) · 2024Article
- Review
- Unraveling the complex interplay between anti-tumor immune response and autoimmunity mediated by B cells and autoantibodies in the era of anti-checkpoint monoclonal antibody therapies.Frontiers in immunology · 2024Review
- Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications.BME frontiers · 2024Review
- IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease.Frontiers in immunology · 2024Review
- Plasma membrane damage limits cytoplasmic delivery by conventional cell penetrating peptides.PloS one · 2024Article
- Targeting Ras with protein engineering.Oncotarget · 2023Review
- Targeting the 'Undruggable' Driver Protein, KRAS, in Epithelial Cancers: Current Perspective.Cells · 2023Review
- Cellular Uptake of Bevacizumab in Cervical and Breast Cancer Cells Revealed by Single-Molecule Spectroscopy.The journal of physical chemistry letters · 2023Article
- KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane.Frontiers in oncology · 2023Article
- Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets.International journal of experimental pathology · 2022Article
- Therapeutic Potential of Intrabodies for Cancer Immunotherapy: Current Status and Future Directions.Antibodies (Basel, Switzerland) · 2022Review
- Antibody-mediated delivery of a viral MHC-I epitope into the cytosol of target tumor cells repurposes virus-specific CD8Molecular cancer · 2022Article
- Targeting the "undruggable" RAS with biologics.Advances in cancer research · 2022Review
- Genetic and Covalent Protein Modification Strategies to Facilitate Intracellular Delivery.Biomacromolecules · 2021Review
- A Patent Review on the Therapeutic Application of Monoclonal Antibodies in COVID-19.International journal of molecular sciences · 2021Review
- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- Demonstration of intracellular trafficking, cytosolic bioavailability, and target manipulation of an antibody delivery platform.Nanomedicine : nanotechnology, biology, and medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Full-length IgG antibodies cannot cross cell membranes of living cells; this limits their use for direct targeting of cytosolic proteins. Here, we describe a general strategy for the generation of intact, full-length IgG antibodies, herein called cytotransmabs, which internalize into living cells and localize in the cytosol. We first generated a humanized light chain variable domain (VL) that could penetrate into the cytosol of living cells and was engineered for association with various subtypes of human heavy chain variable domains (VHs). When light chains with humanized VL were co-expressed with 3 heavy chains (HCs), including 2 HCs of the clinically approved adalimumab (Humira®) and bevacizumab (Avastin®), all 3 purified IgG antibodies were internalized into the cytoplasm of living cells. Cytotransmabs primarily internalized into living cells by the clathrin-mediated endocytic pathway through interactions with heparin sulfate proteoglycan that was expressed on the cell surface. The cytotransmabs escaped into the cytosol from early endosomes without being further transported into other cellular compartments, like the lysosomes, endoplasmic reticulum, Golgi apparatus, and nucleus. Furthermore, we generated a cytotransmab that co-localized with the targeted cytosolic protein when it was incubated with living cells, demonstrating that the cytotransmab can directly target cytosolic proteins. Internalized cytotransmabs did not show any noticeable cytotoxicity and remained in the cytosol for more than 6 h before being degraded by proteosomes. These results suggest that cytotransmabs, which efficiently enter living cells and reach the cytosolic space, will find widespread uses as research, diagnostic, and therapeutic agents.
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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.