ArticleFrontiers in immunology2019
Dual Function pH Responsive Bispecific Antibodies for Tumor Targeting and Antigen Depletion in Plasma.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Discovery and optimization of a pH-responsive ultra-long-acting VHH-based growth hormone mimetic.mAbs · 2026Article
- Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.Journal of hematology & oncology · 2026Review
- Article
- A masking clamp for conditional activation of therapeutic antibodies.Frontiers in immunology · 2025Article
- Prodrug-based bispecific antibodies for cancer therapy: advances and future directions.Frontiers in immunology · 2025Review
- A Competition-Based Strategy for the Isolation of an Anti-Idiotypic Blocking Module and Fine-Tuning for Conditional Activation of a Therapeutic Antibody.Biotechnology journal · 2024Article
- A Conditionally Activated Cytosol-Penetrating Antibody for TME-Dependent Intracellular Cargo Delivery.Antibodies (Basel, Switzerland) · 2024Article
- Balancing the Affinity and Tumor Cell Binding of a Two-in-One Antibody Simultaneously Targeting EGFR and PD-L1.Antibodies (Basel, Switzerland) · 2024Article
- Two in one: the emerging concept of bifunctional antibodies.Current opinion in biotechnology · 2024Review
- Generation of a symmetrical trispecific NK cell engager based on a two-in-one antibody.Frontiers in immunology · 2023Article
- Monoclonal Antibody Engineering and Design to Modulate FcRn Activities: A Comprehensive Review.International journal of molecular sciences · 2022Review
- Yeast Display Guided Selection of pH-Dependent Binders.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization.Frontiers in immunology · 2022Article
- Tumor acidity: From hallmark of cancer to target of treatment.Frontiers in oncology · 2022Review
- Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond.Vaccines · 2021Review
- c-KIT-ERK1/2 signaling activated ELK1 and upregulated carcinoembryonic antigen expression to promote colorectal cancer progression.Cancer science · 2021Article
- pH-responsive antibodies for therapeutic applications.Journal of biomedical science · 2021Review
- Milking the Cow: Cattle-Derived Chimeric Ultralong CDR-H3 Antibodies and Their Engineered CDR-H3-Only Knobbody Counterparts Targeting Epidermal Growth Factor Receptor Elicit Potent NK Cell-Mediated Cytotoxicity.Frontiers in immunology · 2021Article
- Design of a Trispecific Checkpoint Inhibitor and Natural Killer Cell Engager Based on a 2 + 1 Common Light Chain Antibody Architecture.Frontiers in immunology · 2021Article
- Grabbing the Bull by Both Horns: Bovine Ultralong CDR-H3 Paratopes Enable Engineering of 'Almost Natural' Common Light Chain Bispecific Antibodies Suitable For Effector Cell Redirection.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shedding of membrane-bound cell surface proteins, where the extracellular domain is released and found in the circulation is a common phenomenon. A prominent example is CEACAM5 (CEA, CD66e), where the shed domain plays a pivotal role in tumor progression and metastasis. For treatment of solid tumors, the presence of the tumor-specific antigen in the plasma can be problematic since tumor-specific antibodies might be intercepted by the soluble antigen before invading their desired tumor target area. To overcome this problem, we developed a generic procedure to generate bispecific antibodies, where one arm binds the antigen in a pH-dependent manner thereby enhancing antigen clearance upon endosomal uptake, while the other arm is able to target tumor cells pH-independently. This was achieved by incorporating pH-sensitive binding modalities in the common light chain IGKV3-15*01 of a CEACAM5 binding heavy chain only antibody. Screening of a histidine-doped light chain library using yeast surface display enabled the isolation of pH-dependent binders. When such a light chain was utilized as a common light chain in a bispecific antibody format, only the respective heavy/light chain combination, identified during selections, displayed pH-responsive binding. In addition, we found that the altered common light chain does not negatively impact the affinity of other heavy chain only binders toward their respective antigen. Our strategy may open new avenues for the generation of bispecifics, where one arm efficiently removes a shed antigen from the circulation while the other arm targets a tumor marker in a pH-independent manner.
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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.