ArticleJournal for immunotherapy of cancer2019
Bispecific NKG2D-CD3 and NKG2D-CD16 fusion proteins for induction of NK and T cell reactivity against acute myeloid leukemia.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Safety and efficacy of bispecific antibodies in hematologic neoplasms: a systematic review.Frontiers in immunology · 2026Pooled it
- Targeting NKG2D/NKG2DL axis in cancer immunotherapy: mechanisms and therapeutic applications.Journal of translational medicine · 2026Review
- Bispecific Nanosystems Enable Multieffector Immune Cell Retargeting for Hematologic Malignancy Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Bispecific killer engager for targeted depletion of PD-1 positive lymphocytes: A new avenue for autoimmune disease treatment.Acta pharmaceutica Sinica. B · 2025Article
- Fc-optimized CD276 antibody enhances NK cell activation against non-small cell lung cancer.Frontiers in immunology · 2025Article
- Heterogeneity of γδ T-cell subsets and their clinical correlation in patients with AML.Frontiers in immunology · 2025Article
- Targeting CD276 for T cell-based immunotherapy of breast cancer.Journal of translational medicine · 2024Article
- Targeting NKG2D ligands in glioblastoma with a bispecific T-cell engager is augmented with conventional therapy and enhances oncolytic virotherapy of glioma stem-like cells.Journal for immunotherapy of cancer · 2024Article
- Induction of NK cell reactivity against acute myeloid leukemia by Fc-optimized CD276 (B7-H3) antibody.Blood cancer journal · 2024Article
- Selective lysis of acute myeloid leukemia cells by CD34/CD3 bispecific antibody through the activation of γδ T-cells.Oncoimmunology · 2024Article
- Targeting NKG2DL with Bispecific NKG2D-CD16 and NKG2D-CD3 Fusion Proteins on Triple-Negative Breast Cancer.International journal of molecular sciences · 2023Article
- Advances in NK cell therapy for hematologic malignancies: NK source, persistence and tumor targeting.Blood reviews · 2023Review
- Bispecific NK-cell engager targeting BCMA elicits stronger antitumor effects and produces less proinflammatory cytokines than T-cell engager.Frontiers in immunology · 2023Article
- Novel NKG2D-directed bispecific antibodies enhance antibody-mediated killing of malignant B cells by NK cells and T cells.Frontiers in immunology · 2023Article
- The Latest Breakthroughs in Immunotherapy for Acute Myeloid Leukemia, with a Special Focus on NKG2D Ligands.International journal of molecular sciences · 2022Review
- Natural killer cells and acute myeloid leukemia: promises and challenges.Cancer immunology, immunotherapy : CII · 2022Review
- Multi-omics profiling identifies C1QA/BAnnals of translational medicine · 2022Article
- Platelets subvert antitumor efficacy of T cell-recruiting bispecific antibodies.Journal for immunotherapy of cancer · 2022Article
- B7-H3-targeting Fc-optimized antibody for induction of NK cell reactivity against sarcoma.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMonoclonal antibodies (mAbs) mediate their effects in great part by inducing ADCC of NK cells, and multiple efforts aim to increase this function by engineering mAbs optimized Fc-parts. Even more potent antitumor immunity can be induced by strategies to stimulate T cells with their profoundly higher effector potential. However, upon increased immunostimulatory potential, the necessity to target highly tumor-specific antigens becomes critically important to reduce side effects.
methodsWe here report on bispecific fusion proteins (BFP) that target ligands of the immunoreceptor NKG2D (NKG2DL), which are widely expressed on malignant cells but generally absent on healthy tissue. They consist of the extracellular domain of NKG2D as targeting moiety fused to Fab-fragments of CD3 (NKG2D-CD3) or CD16 (NKG2D-CD16) antibodies.
resultsNKG2D-CD16 displayed increased affinity to the FcγRIII on NK cells compared to engineered Fc-parts, which are contained in optimized mAbs that presently undergo clinical evaluation. In line, NKG2D-CD16 induced superior activation, degranulation, IFN-γ production and lysis of acute myeloid leukemia (AML) cell lines and patient AML cells. NKG2D-CD3 in turn potently stimulated T cells, and comparison of efficacy over time revealed that NKG2D-CD16 was superior upon short term application, while NKG2D-CD3 mediated overall more potent effects which manifested after longer times. This can be attributed to treatment-induced proliferation of T cells but not NK cells.
conclusionsTaken together, we here introduce novel "antibody-like" BFP that take advantage of the highly tumor-restricted expression of NKG2DL and potently activate the reactivity of NK cells or T cells for immunotherapy of AML.
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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.