ArticleJournal for immunotherapy of cancer2024
Bispecific immune cell engager enhances the anticancer activity of CD16+ NK cells and macrophages in vitro, and eliminates cancer metastasis in NK humanized NOG mice.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 15 citations in OpenAlex.
- Determinants of Response to Sequential Pembrolizumab with Trastuzumab plus Platinum/5-FU in HER2-Positive Gastric Cancer: A Phase II Chemoimmunotherapy Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- EGFR-Targeting IgG1 Antibody Enhances NK Cell-Mediated Tumor Killing in KRAS-Mutant Pancreatic Cancer.MedComm · 2026Article
- Stem cell-directed targeted chemotherapy primes drug-resistant metastatic ovarian tumors for elimination by natural killer cells.Molecular therapy. Oncology · 2026Article
- Advancement of humanized mice and leading applications in immunological disease models.Inflammation and regeneration · 2026Review
- The PPTC7/BNIP3/NIX axis induces cGAS/STING-mediated senescence and augments CAR-T efficacy by repressing tumor-intrinsic mitophagy.Journal of experimental & clinical cancer research : CR · 2026Article
- RNF216 as a Promising Biomarker for Prognosis, Immunotherapy, and Chemotherapy in LIHC: A Comprehensive Pan-Cancer Analysis and Experimental Validation.Journal of Cancer · 2026Article
- A new era of natural killer cell immunotherapy in tumor treatment: latest advances and cutting-edge perspectives from basic research to clinical practice.Frontiers in immunology · 2026Review
- Natural Killer Cell Therapy in Ovarian Cancer: From Preclinical Potentials to Clinical Applications and Combination Strategies.International journal of biological sciences · 2026Review
- The Role of Tenascin-C in Neuroinflammation and Neuroplasticity.International journal of molecular sciences · 2025Review
- Leveraging liquid biopsy to uncover resistance mechanisms and guide personalized immunotherapy.Translational oncology · 2025Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 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
- T-Cell Engager Therapy in Prostate Cancer: Molecular Insights into a New Frontier in Immunotherapy.Cancers · 2025Review
- Bispecific Antibodies, Nanobodies and Extracellular Vesicles: Present and Future to Cancer Target Therapy.Biomolecules · 2025Review
- NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025Review
- The broad spectrum of cancer and immunotherapy: achievements and limitations.Frontiers in immunology · 2025Review
- Current Developments in NK Cell Engagers for Cancer Immunotherapy: Focus on CD16A and NKp46.Immune network · 2024Review
- A Novel Tetravalent Bispecific Immune Cell Engager Activates Natural Killer Cells to Kill Cancer Cells without Mediating Fratricide.Antibodies (Basel, Switzerland) · 2024Article
- Natural killer cell engagers for cancer immunotherapy.Frontiers in oncology · 2024Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn a prior report, we detailed the isolation and engineering of a bispecific killer cell engager, referred to as BiKE:E5C1. The BiKE:E5C1 exhibits high affinity/specificity for the CD16a activating receptor on natural killer (NK) cells and human epidermal growth factor receptor 2 (HER2) on cancer cells. In vitro studies have demonstrated that BiKE:E5C1 can activate the NK cells and induce the killing of HER2+ ovarian and breast cancer cells, surpassing the performance of the best-in-class monoclonal antibody, Trazimera (trastuzumab). To advance this BiKE technology toward clinical application, the objective of this research was to demonstrate the ability of BiKE:E5C1 to activate CD16+ immune cells such as NK cells and macrophages to kill cancer cells, and eradicate metastatic HER2+ tumors in NK humanized NOG mice.
methodsWe assessed BiKE:E5C1's potential to activate CD16-expressing peripheral blood (PB)-NK cells, laNK92 cells, and THP-1-CD16A monocyte-macrophages through flowcytometry and antibody-dependent cell-mediated cytotoxicity/phagocytosis (ADCC) assays. Subsequently, laNK92 cells were selected as effector cells and genetically modified to express the nanoluciferase gene, enabling the monitoring of their viability in NK humanized NOG mice using quantitative bioluminescent imaging (qBLI). To evaluate the functionality of BiKE:E5C1 in vivo, we introduced firefly luciferase-expressing ovarian cancer cells via intraperitoneal injection into hIL-15 and hIL-2 NOG mice, creating a model of ovarian cancer metastasis. Once tumor establishment was confirmed, we treated the mice with laNK92 cells plus BiKE:E5C1 and the response to therapy was assessed using qBLI.
resultsOur data demonstrate that BiKE:E5C1 activates not only laNK92 cells but also PB-NK cells and macrophages, significantly enhancing their anticancer activities. ADCC assay demonstrated that IgG
conclusionsCollectively, our in vivo findings underscore BiKE:E5C1's potential as an immune cell engager capable of activating immune cells for cancer cell elimination, thereby expanding the arsenal of available BiKEs for cancer immunotherapy.
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