ArticleFrontiers in immunology2018
Expression of a Recombinant High Affinity IgG Fc Receptor by Engineered NK Cells as a Docking Platform for Therapeutic mAbs to Target Cancer Cells.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 80 citations in OpenAlex.
- Afucosylated VAR2CSA-Specific IgG Reduces Risks of Placental Malaria.The Journal of infectious diseases · 2026Article
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- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- CAR-NK cell therapy for hematological malignancies.Blood advances · 2026Review
- Human CD3 complex is required for the generation of T-cell receptor-like chimeric antigen receptor targeting WT1 in natural killer cells.Cancer immunology, immunotherapy : CII · 2026Article
- Induced pluripotent stem cells as platforms for engineering NK cell immunotherapies.Frontiers in cell and developmental biology · 2026Review
- Engineering multi-specific nano-antibodies for cancer immunotherapy.Nature biomedical engineering · 2025Article
- State of the Art of CAR-NK Cell Therapy in Multiple Myeloma: A Comprehensive Review of Cell Sources and Target Antigens.International journal of molecular sciences · 2025Review
- CAR NK cell therapy for solid tumors: potential and challenges.Antibody therapeutics · 2025Review
- Fc-Afucosylation of VAR2CSA-Specific Immunoglobulin G and Clinical Immunity to Placental Plasmodium falciparum Malaria.The Journal of infectious diseases · 2025Article
- Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications.Life medicine · 2025Review
- Gene-modified NK cells expressing CD64 and preloaded with HIV-specific BNAbs target autologous HIV-1-infected CD4+ T cells by ADCC.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Adoptive Cell Therapy from the Dish: Potentiating Induced Pluripotent Stem Cells.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria.Nature communications · 2025Article
- Application and prospects of genetic engineering in CAR-NK cell therapy.Frontiers in immunology · 2025Review
- CAR-NK cell therapy: promise and challenges in solid tumors.Frontiers in immunology · 2025Review
- Distinct CD16a features on human NK cells observed by flow cytometry correlate with increased ADCC.Scientific reports · 2024Article
- A highly efficient transgene knock-in technology in clinically relevant cell types.Nature biotechnology · 2024Article
- CAR-mediated targeting of NK cells overcomes tumor immune escape caused by ICAM-1 downregulation.Journal for immunotherapy of cancer · 2024Article
- iPSC-derived NK cells expressing high-affinity IgG Fc receptor fusion CD64/16A to mediate flexible, multi-tumor antigen targeting for lymphoma.Frontiers in immunology · 2024Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Anti-tumor mAbs are the most widely used and characterized cancer immunotherapy. Despite having a significant impact on some malignancies, most cancer patients respond poorly or develop resistance to this therapy. A known mechanism of action of these therapeutic mAbs is antibody-dependent cell-mediated cytotoxicity (ADCC), a key effector function of human NK cells. CD16A on human NK cells has an exclusive role in binding to tumor-bound IgG antibodies. Though CD16A is a potent activating receptor, it is also a low affinity IgG Fc receptor (FcγR) that undergoes a rapid downregulation in expression by a proteolytic process involving ADAM17 upon NK cell activation. These regulatory processes are likely to limit the efficacy of tumor-targeting therapeutic mAbs in the tumor environment. We sought to enhance NK cell binding to anti-tumor mAbs by engineering these cells with a recombinant FcγR consisting of the extracellular region of CD64, the highest affinity FcγR expressed by leukocytes, and the transmembrane and cytoplasmic regions of CD16A. This novel recombinant FcγR (CD64/16A) was expressed in the human NK cell line NK92 and in induced pluripotent stem cells from which primary NK cells were derived. CD64/16A lacked the ADAM17 cleavage region in CD16A and it was not rapidly downregulated in expression following NK cell activation during ADCC. CD64/16A on NK cells facilitated conjugation to antibody-treated tumor cells, ADCC, and cytokine production, demonstrating functional activity by its two components. Unlike NK cells expressing CD16A, CD64/16A captured soluble therapeutic mAbs and the modified NK cells mediated tumor cell killing. Hence, CD64/16A could potentially be used as a docking platform on engineered NK cells for therapeutic mAbs and IgG Fc chimeric proteins, allowing for switchable targeting elements and a novel cancer cellular therapy.
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