ArticleFrontiers in immunology2022
Dual Fc optimization to increase the cytotoxic activity of a CD19-targeting antibody.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Myeloid cell-mediated killing of B-ALL by CD38 and CD20 IgA antibody variants is enhanced by CD47/SIRPα interference.Blood neoplasia · 2026Article
- Combination of Fc-Protein Engineering Strategies: Design and Evaluation of Antibody Effector Functions.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics.Archives of pharmacal research · 2026Review
- Review
- Memory-like Natural Killer Cell and CD19 Antibody-Based Immunotherapy in Combination with Tyrosine Kinase Inhibition Has Antitumor Effects against Ph(-like) Acute Lymphoblastic Leukemia.Cancer immunology research · 2025Article
- Tumor-restricted activation of Vγ9Vδ2 T cells via bispecific Evobodies: a novel strategy for safe and potent immunotherapy in ovarian cancer.Frontiers in immunology · 2025Article
- Cytokine-induced memory-like NK cells combined with Tafasitamab demonstrate efficacy against B-cell acute lymphoblastic leukemia.Immunotherapy advances · 2025Article
- Unlocking the Power of Complement-Dependent Cytotoxicity: Engineering Strategies for the Development of Potent Therapeutic Antibodies for Cancer Treatments.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- In Vitro Diffuse Large B-Cell Lymphoma Cell Line Models as Tools to Investigate Novel Immunotherapeutic Strategies.Cancers · 2022Review
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting CD19 represents a promising strategy for the therapy of B-cell malignancies. Although non-engineered CD19 antibodies are poorly effective in mediating complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP), these effector functions can be enhanced by Fc-engineering. Here, we engineered a CD19 antibody with the aim to improve effector cell-mediated killing and CDC activity by exchanging selected amino acid residues in the Fc domain. Based on the clinically approved Fc-optimized antibody tafasitamab, which triggers enhanced ADCC and ADCP due to two amino acid exchanges in the Fc domain (S239D/I332E), we additionally added the E345K amino acid exchange to favor antibody hexamerization on the target cell surface resulting in improved CDC. The dual engineered CD19-DEK antibody bound CD19 and Fcγ receptors with similar characteristics as the parental CD19-DE antibody. Both antibodies were similarly efficient in mediating ADCC and ADCP but only the dual optimized antibody was able to trigger complement deposition on target cells and effective CDC. Our data provide evidence that from a technical perspective selected Fc-enhancing mutations can be combined (S239D/I332E and E345K) allowing the enhancement of ADCC, ADCP and CDC with isolated effector populations. Interestingly, under more physiological conditions when the complement system and FcR-positive effector cells are available as effector source, strong complement deposition negatively impacts FcR engagement. Both effector functions were simultaneously active only at selected antibody concentrations. Dual Fc-optimized antibodies may represent a strategy to further improve CD19-directed cancer immunotherapy. In general, our results can help in guiding optimal antibody engineering strategies to optimize antibodies' effector functions.
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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.