ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Enhanced ADCC and NK Cell Activation of an Anticarcinoma Bispecific Antibody by Genetic Insertion of a Modified IL-15 Cross-linker.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 89 citations in OpenAlex.
- EGFRxCD16 bispecific antibodies orchestrate superior NK cell-mediated lysis of ovarian cancer and NSCLC cell lines in combination with oncolytic viruses.Cancer immunology, immunotherapy : CII · 2026Article
- Advances in IL-15-Based Cancer Immunotherapy and Divergent Immunological Effects of IL-2 and IL-15 Signaling via the Shared IL-2Rβγ Receptor.Frontiers in immunology · 2026Review
- Therapeutic reprogramming of natural killer cells for solid tumors: expanding frontiers into rare and ultra-rare malignancies.Frontiers in molecular biosciences · 2026Review
- Advances in augmenting infiltration of active natural killer cells into pediatric and adult solid tumors.Molecular therapy. Oncology · 2025Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- A nanobody-based tri-specific NK cell engager targeting CD5 triggers antitumor immunity.Cell reports. Medicine · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Improving CD3 bispecific antibody therapy in solid tumors using combination strategies.Frontiers in oncology · 2025Review
- T-Cell redirecting bispecific antibodies: a review of a novel class of immuno-oncology for advanced prostate cancer.Cancer biology & therapy · 2024Review
- Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer.Journal of experimental & clinical cancer research : CR · 2024Review
- Reprogramming natural killer cells for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Review
- Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager.Molecules (Basel, Switzerland) · 2024Article
- Tri-specific killer engager: unleashing multi-synergic power against cancer.Exploration of targeted anti-tumor therapy · 2024Review
- Chimeric antigen receptor-natural killer cells: a promising sword against insidious tumor cells.Human cell · 2023Review
- Principles and current clinical landscape of NK cell engaging bispecific antibody against cancer.Human vaccines & immunotherapeutics · 2023Review
- Mapping the interplay between NK cells and HIV: therapeutic implications.Journal of leukocyte biology · 2023Review
- When three is not a crowd: trispecific antibodies for enhanced cancer immunotherapy.Theranostics · 2023Review
- Understanding the versatile roles and applications of EpCAM in cancers: from bench to bedside.Experimental hematology & oncology · 2022Review
- Chimeric antigen receptor-engineered NK cells: new weapons of cancer immunotherapy with great potential.Experimental hematology & oncology · 2022Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Previously, we constructed a bispecific NK-cell-engager (BiKE) bearing single-chain variable fragments (scFv) against CD16 on NK cells and EpCAM on tumor cells. This BiKE facilitated antigen-specific antibody-dependent cell-mediated cytotoxicity (ADCC) but did not induce NK cell expansion. We incorporated a modified interleukin-15 cross-linker to create a trispecific construct (TriKE) in order to improve activation, proliferation, and survival of NK cells. Synthesis and assembly of hybrid genes encoding the TriKE was accomplished using DNA-shuffling and DNA-ligation techniques. The TriKE was tested for specificity, efficacy, proliferative capability, and cytokine profile using functional assays. The molecular modifications improved yield without compromising binding to EpCAM(+) HT-29 colorectal carcinoma cells. (51)Chromium-release and degranulation assays showed better killing rates with TriKE compared to BiKE. TriKE was more active in a variety of different carcinoma cell lines. TriKE showed the ability to stimulate expansion of CD56(+)CD3(-) NK cells. BiKE and TriKE showed enhanced but not supraphysiologic levels of cytokine secretion. 1615EpCAM TriKE drives enhanced ADCC while significantly improving proliferation, activation, and survival of NK cell effectors. The TriKE provides a selectively delivered self-sustaining signal at the NK/tumor cell synapse. Targeted cytokine stimulation, rather than systemic cytokine administration, may impact toxicity in patients rendering the TriKE a promising new off-the-shelf carcinoma therapy.
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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.