ArticlePloS one2013
EGFR-targeted granzyme B expressed in NK cells enhances natural cytotoxicity and mediates specific killing of tumor cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Modern Advances in CARs Therapy and Creating a New Approach to Future Treatment.International journal of molecular sciences · 2022Review
- Advances in epidermal growth factor receptor specific immunotherapy: lessons to be learned from armed antibodies.Oncotarget · 2020Review
- Article
- Engineering Thermo-pH Dual Responsive Hydrogel for Enhanced Tumor Accumulation, Penetration, and Chemo-Protein Combination Therapy.International journal of nanomedicine · 2020Article
- Development of a human immuno-oncology therapeutic agent targeting HER2: targeted delivery of granzyme B.Journal of experimental & clinical cancer research : CR · 2019Article
- Synergistic effect of granzyme B-azurin fusion protein on breast cancer cells.Molecular biology reports · 2019Article
- Review
- Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic DrugAsian Pacific journal of cancer prevention : APJCP · 2018Article
- Cetuximab combined with natural killer cells therapy: an alternative to chemoradiotherapy for patients with advanced non-small cell lung cancer (NSCLC).American journal of cancer research · 2018Article
- Targeting of Tumor Neovasculature with GrB/VEGFBiomedicines · 2017Review
- Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity.Frontiers in immunology · 2017Article
- Article
- T-cell and natural killer cell therapies for hematologic malignancies after hematopoietic stem cell transplantation: enhancing the graft-versus-leukemia effect.Haematologica · 2015Review
- Antimalarial activity of granzyme B and its targeted delivery by a granzyme B-single-chain Fv fusion protein.Antimicrobial agents and chemotherapy · 2015Article
- Arming NK cells with enhanced antitumor activity: CARs and beyond.Oncoimmunology · 2013Article
- Immunopotentiation effects of apigenin on NK cell proliferation and killing pancreatic cancer cells.International journal of immunopathology and pharmacologyArticle
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells are highly specialized effectors of the innate immune system that hold promise for adoptive cancer immunotherapy. Their cell killing activity is primarily mediated by the pro-apoptotic serine protease granzyme B (GrB), which enters targets cells with the help of the pore-forming protein perforin. We investigated expression of a chimeric GrB fusion protein in NK cells as a means to augment their antitumoral activity. For selective targeting to tumor cells, we fused the epidermal growth factor receptor (EGFR) peptide ligand transforming growth factor α (TGFα) to human pre-pro-GrB. Established human NKL natural killer cells transduced with a lentiviral vector expressed this GrB-TGFα (GrB-T) molecule in amounts comparable to endogenous wildtype GrB. Activation of the genetically modified NK cells by cognate target cells resulted in the release of GrB-T together with endogenous granzymes and perforin, which augmented the effector cells' natural cytotoxicity against NK-sensitive tumor cells. Likewise, GrB-T was released into the extracellular space upon induction of degranulation with PMA and ionomycin. Secreted GrB-T fusion protein displayed specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Our data demonstrate that ectopic expression of a targeted GrB fusion protein in NK cells is feasible and can enhance antitumoral activity of the effector cells.
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