ArticlemAbs
Impact of antibody architecture and paratope valency on effector functions of bispecific NKp30 x EGFR natural killer cell engagers.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Engineering immune cell engagers: From molecular constructs to biomaterial platforms.Materials today. Bio · 2026Review
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- Simultaneous targeting of IL-10 and PD-(L)1 pathways with a bispecific anti-PD-L1/IL-10-trap antibody enhances T cell responses.Molecular therapy. Oncology · 2026Article
- Engineering NKG2D ligand affinity transforms EGFR-targeted NK cell engagers into high-potency effectors against pancreatic cancer.Journal of biological engineering · 2026Article
- Smart Nanoformulations for Oncology: A Review on Overcoming Biological Barriers with Active Targeting, Stimuli-Responsive, and Controlled Release for Effective Drug Delivery.Pharmaceutics · 2026Review
- Natural Killer Cell Therapy in Ovarian Cancer: From Preclinical Potentials to Clinical Applications and Combination Strategies.International journal of biological sciences · 2026Review
- Article
- Review
- NKp30: A Key Membrane Molecule in the Fight Against Cancer and Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Killing the killers: Natural killer cell therapy targeting glioma stem cells in high-grade glioma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Enhancing NK cell-mediated tumor killing of B7-H6Molecular therapy. Oncology · 2025Article
- Taming interleukin-12: Engineering of bispecific antibody-based IL-12 mimetics with biased agonism capacities.Protein science : a publication of the Protein Society · 2025Article
- On the humanization of VHHs: Prospective case studies, experimental and computational characterization of structural determinants for functionality.Protein science : a publication of the Protein Society · 2024Article
- Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance.International journal of molecular sciences · 2024Review
- An engineered NKp46 antibody for construction of multi-specific NK cell engagers.Protein engineering, design & selection : PEDS · 2024Article
- Natural killer cell engagers for cancer immunotherapy.Frontiers in oncology · 2024Review
- Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Natural killer (NK) cells emerged as a promising effector population that can be harnessed for anti-tumor therapy. In this work, we constructed NK cell engagers (NKCEs) based on NKp30-targeting single domain antibodies (sdAbs) that redirect the cytotoxic potential of NK cells toward epidermal growth factor receptor (EGFR)-expressing tumor cells. We investigated the impact of crucial parameters such as sdAb location, binding valencies, the targeted epitope on NKp30, and the overall antibody architecture on the redirection capacity. Our study exploited two NKp30-specific sdAbs, one of which binds a similar epitope on NKp30 as its natural ligand B7-H6, while the other sdAb addresses a non-competing epitope. For EGFR-positive tumor targeting, humanized antigen-binding domains of therapeutic antibody cetuximab were used. We demonstrate that NKCEs bivalently targeting EGFR and bivalently engaging NKp30 are superior to monovalent NKCEs in promoting NK cell-mediated tumor cell lysis and that the architecture of the NKCE can substantially influence killing capacities depending on the NKp30-targeting sdAb utilized. While having a pronounced impact on NK cell killing efficacy, the capabilities of triggering antibody-dependent cellular phagocytosis or complement-dependent cytotoxicity were not significantly affected comparing the bivalent IgG-like NKCEs with cetuximab. However, the fusion of sdAbs can have a slight impact on the NK cell release of immunomodulatory cytokines, as well as on the pharmacokinetic profile of the NKCE due to unfavorable spatial orientation within the molecule architecture. Ultimately, our findings reveal novel insights for the engineering of potent NKCEs triggering the NKp30 axis.
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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.