ArticleFrontiers in immunology2021
Design of a Trispecific Checkpoint Inhibitor and Natural Killer Cell Engager Based on a 2 + 1 Common Light Chain Antibody Architecture.
Article in Frontiers in immunology, 2021. 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, 30 citations in OpenAlex.
- Fc-Silenced CD89 × EGFR Bispecific Antibodies Promote Neutrophil and Macrophage Antitumor Activity.Antibodies (Basel, Switzerland) · 2026Article
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Smart Nanoformulations for Oncology: A Review on Overcoming Biological Barriers with Active Targeting, Stimuli-Responsive, and Controlled Release for Effective Drug Delivery.Pharmaceutics · 2026Review
- Revolutionizing cancer immunotherapy: T cell engagers beyond hematologic malignancies toward solid tumors.Frontiers in immunology · 2026Review
- Natural killer cell-based immunotherapy for cancer.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Trispecific eFab-eIg T-cell engagers targeting HER2 and HER3.Frontiers in immunology · 2025Article
- Facile Access to Branched Multispecific Proteins.Bioconjugate chemistry · 2024Article
- Balancing the Affinity and Tumor Cell Binding of a Two-in-One Antibody Simultaneously Targeting EGFR and PD-L1.Antibodies (Basel, Switzerland) · 2024Article
- Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager.Molecules (Basel, Switzerland) · 2024Article
- Tri-specific killer engager: unleashing multi-synergic power against cancer.Exploration of targeted anti-tumor therapy · 2024Review
- Natural killer cell engagers for cancer immunotherapy.Frontiers in oncology · 2024Review
- Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors.Cancer communications (London, England) · 2023Review
- Natural Killer Cell Engagers (NKCEs): a new frontier in cancer immunotherapy.Frontiers in immunology · 2023Review
- When three is not a crowd: trispecific antibodies for enhanced cancer immunotherapy.Theranostics · 2023Review
- Generation of a symmetrical trispecific NK cell engager based on a two-in-one antibody.Frontiers in immunology · 2023Article
- T cells, NK cells, and tumor-associated macrophages in cancer immunotherapy and the current state of the art of drug delivery systems.Frontiers in immunology · 2023Review
- Conditional activation of an anti-IgM antibody-drug conjugate for precise B cell lymphoma targeting.Frontiers in immunology · 2023Article
- Targeted Phagocytosis Induction for Cancer Immunotherapy via Bispecific MerTK-Engaging Antibodies.International journal of molecular sciences · 2022Article
- Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody.Immune network · 2022Review
- TriTECM: A tetrafunctional T-cell engaging antibody with built-in risk mitigation of cytokine release syndrome.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer cell engagers gained enormous interest in recent years due to their potent anti-tumor activity and favorable safety profile. Simultaneously, chicken-derived antibodies entered clinical studies paving the way for avian-derived therapeutics. In this study, we describe the affinity maturation of a common light chain (cLC)-based, chicken-derived antibody targeting EGFR, followed by utilization of the same light chain for the isolation of CD16a- and PD-L1-specific monoclonal antibodies. The resulting binders target their respective antigen with single-digit nanomolar affinity while blocking the ligand binding of all three respective receptors. Following library-based humanization, bispecific and trispecific variants in a standard 1 + 1 or a 2 + 1 common light chain format were generated, simultaneously targeting EGFR, CD16a, and PD-L1. The trispecific antibody mediated an elevated antibody-dependent cellular cytotoxicity (ADCC) in comparison to the EGFR×CD16a bispecific variant by effectively bridging EGFR/PD-L1 double-positive cancer cells with CD16a-positive effector cells. These findings represent, to our knowledge, the first detailed report on the generation of a trispecific 2 + 1 antibodies exhibiting a common light chain and illustrate synergistic effects of trispecific antigen binding. Overall, this generic procedure paves the way for the engineering of tri- and oligospecific therapeutic antibodies derived from avian immunizations.
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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.