ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 x 33 bispecific killer cell engager and ADAM17 inhibition.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 217 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Engineering immune cell engagers: From molecular constructs to biomaterial platforms.Materials today. Bio · 2026Review
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
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- Review
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- Building a better natural killer (NK) cell: Fc receptor engineering strategies for NK cell therapeutics.Future virology · 2025Article
- CD16A Shedding Regulates Innate Cell Engager-Induced Serial Killing by Natural Killer Cells.European journal of immunology · 2025Article
- Next-generation immunotherapeutic approaches for blood cancers: Exploring the efficacy of CAR-T and cancer vaccines.Experimental hematology & oncology · 2025Review
- The rewired immune microenvironment in leukemia.Nature immunology · 2025Review
- PD-1 Bispecific Killer Engager (PD-1 BiKE) effectively depletes effector T lymphocytes in experimental autoimmune encephalomyelitis.Frontiers in immunology · 2025Article
- Enhancing Therapeutic Efficacy of FLT3 Inhibitors with Combination Therapy for Treatment of Acute Myeloid Leukemia.International journal of molecular sciences · 2024Review
- Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.Pharmaceutics · 2024Review
- The Immune Resistance Signature of Acute Myeloid Leukemia and Current Immunotherapy Strategies.Cancers · 2024Review
- Natural killer cell therapies.Nature · 2024Review
- Review
- Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers.Science advances · 2023Article
- Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe graft versus leukemia effect by natural killer (NK) cells prevents relapse following hematopoietic stem cell transplantation. We determined whether a novel bispecific killer cell engager (BiKE) signaling through CD16 and targeting CD33 could activate NK cells at high potency against acute myelogenous leukemia (AML) targets. EXPERIMENTAL
designWe investigated the ability of our fully humanized CD16 × CD33 (CD16 × 33) BiKE to trigger in vitro NK cell activation against HL60 (CD33(+)), RAJI (CD33(-)), and primary AML targets (de novo and refractory) to determine whether treatment with CD16 × 33 BiKE in combination with an ADAM17 inhibitor could prevent CD16 shedding (a novel inhibitory mechanism induced by NK cell activation) and overcome inhibition of class I MHC recognizing inhibitory receptors.
resultsNK cell cytotoxicity and cytokine release were specifically triggered by the CD16 × 33 BiKE when cells were cultured with HL60 targets, CD33(+) de novo and refractory AML targets. Combination treatment with CD16 × 33 BiKE and ADAM17 inhibitor resulted in inhibition of CD16 shedding in NK cells, and enhanced NK cell activation. Treatment of NK cells from double umbilical cord blood transplant (UCBT) recipients with the CD16 × 33 BiKE resulted in activation, especially in those recipients with cytomegalovirus reactivation.
conclusionCD16 × 33 BiKE can overcome self-inhibitory signals and effectively elicit NK cell effector activity against AML. These in vitro studies highlight the potential of CD16 × 33 BiKE ± ADAM17 inhibition to enhance NK cell activation and specificity against CD33(+) AML, which optimally could be applied in patients with relapsed AML or for adjuvant antileukemic therapy posttransplantation.
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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.