ArticleBlood advances2018
161533 TriKE stimulates NK-cell function to overcome myeloid-derived suppressor cells in MDS.
Article in Blood advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Engineering cytokines for cancer immunotherapy: a systematic review.Frontiers in immunology · 2023Pooled it
- Recent advances of cell therapies for AML/MDS: exploring the therapeutic potential of innate immune cells in AML/MDS.International journal of hematology · 2026Review
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- HIV tri-specific killer engagers directly enhance NK cell function and safely expand NK cells in vivo.Cell reports. Medicine · 2026Article
- ITPKB is a conserved regulator of natural killer cell desensitization/education that constrains antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Review
- Leukemia-targeting NK cell nanoengagers effectively promote robust NK activation and potent anti-acute myeloid leukemia response.Journal of nanobiotechnology · 2026Article
- Prospects and limitations of NK cell adoptive therapy in clinical applications.Cancer metastasis reviews · 2025Review
- Fragment-Based Immune Cell Engager Antibodies in Treatment of Cancer, Infectious and Autoimmune Diseases: Lessons and Insights from Clinical and Translational Studies.Antibodies (Basel, Switzerland) · 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
- A PSMA-Targeted Tri-Specific Killer Engager Enhances NK Cell Cytotoxicity against Prostate Cancer.Cancer immunology research · 2025Article
- Bispecific immunotherapy based on antibodies, T-cell receptors, and aptamers: mechanisms of action, adverse effects, and future perspectives.Frontiers in immunology · 2025Review
- CLEC12A-directed immunocytokine with target cell-restricted IL-15 activity for treatment of acute myeloid leukemia.Frontiers in immunology · 2025Article
- MDSC: a new potential breakthrough in CAR-T therapy for solid tumors.Cell communication and signaling : CCS · 2024Review
- Natural killer cell engagers: From bi-specific to tri-specific and tetra-specific engagers for enhanced cancer immunotherapy.Clinical and translational medicine · 2024Review
- Current Insights into CAR T-Cell-Based Therapies for Myelodysplastic Syndrome.Pharmaceutical research · 2024Review
- Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.Pharmaceutics · 2024Review
- Emerging Innate Immune Cells in Cancer Immunotherapy: Promises and Challenges.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Therapeutic approaches to enhance natural killer cell cytotoxicity.Frontiers in immunology · 2024Review
- Multimeric immunotherapeutic complexes activating natural killer cells towards HIV-1 cure.Journal of translational medicine · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Myelodysplastic syndrome (MDS) is a clonal heterogeneous stem cell disorder driven by multiple genetic and epigenetic alterations resulting in ineffective hematopoiesis. MDS has a high frequency of immune suppressors, including myeloid-derived suppressor cells (MDSCs), that collectively result in a poor immune response. MDSCs in MDS patients express CD155 that ligates the T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and delivers an inhibitory signal to natural killer (NK) cells. To mediate a productive immune response against MDS, negative regulatory checkpoints, like TIGIT, expressed on MDS NK cells must be overcome. NK cells can be directed to lyse MDS cells by bispecific killer engagers (BiKEs) that ligate CD16 on NK cells and CD33 on MDS cells. However, such CD16 × CD33 (1633) BiKEs do not induce the proliferative response in MDS NK cells needed to sustain their function. Here, we show that the addition of an NK stimulatory cytokine, interleukin-15 (IL-15), into the BiKE platform leads to productive IL-15 signaling without TIGIT upregulation on NK cells from MDS patients. Lower TIGIT expression allowed NK cells to resist MDSC inhibition. When compared with 1633 BiKE, 161533 trispecific killer engager (TriKE)-treated NK cells demonstrated superior killing kinetics associated with increased STAT5 phosphorylation. Furthermore, 161533 TriKE-treated MDS NK cells had higher proliferation and enhanced NK-cell function than 1633 BiKE-treated cells without the IL-15 linker. Collectively, our data demonstrate novel characteristics of the 161533 TriKE that support its application as an immunotherapeutic agent for MDS patients.
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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.