C-type lectin-like molecule-1 (CLL1)-targeted TRAIL augments the tumoricidal activity of granulocytes and potentiates therapeutic antibody-dependent cell-mediated cytotoxicity
| Autor: | Yunwei Wei, Valerie R. Wiersma, Marloes J. M. Gooden, Wijnand Helfrich, Djoke Hendriks, Hans W. Nijman, Douwe F. Samplonius, Jin Zhou, Maartje C.A. Wouters, Marco de Bruyn, Ce Shi, Edwin Bremer |
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| Přispěvatelé: | Targeted Gynaecologic Oncology (TARGON), Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL) |
| Rok vydání: | 2015 |
| Předmět: |
Male
MONOCLONAL-ANTIBODY Antibodies Neoplasm medicine.drug_class medicine.medical_treatment Immunology TRAIL STRAIL FUSION PROTEIN Granulocyte Monoclonal antibody TNF-Related Apoptosis-Inducing Ligand Neoplasms medicine ANTICANCER ACTIVITY Humans Immunology and Allergy Cytotoxic T cell Lectins C-Type CANCER-CELLS IMMUNOTHERAPY Cytotoxicity antibody-therapy NEUTROPHILS Antibody-dependent cell-mediated cytotoxicity RECEPTOR biology APOPTOSIS-INDUCING LIGAND Chemistry INDUCTION CLL1 Antibody-Dependent Cell Cytotoxicity Membrane Proteins U937 Cells Immunotherapy COLONY-STIMULATING FACTOR Killer Cells Natural medicine.anatomical_structure granulocyte biology.protein Cancer research Female Tumor necrosis factor alpha Antibody ADCC leukocyte Granulocytes Reports |
| Zdroj: | mAbs, 7(2), 321-330 |
| ISSN: | 1942-0870 1942-0862 |
| DOI: | 10.1080/19420862.2015.1007811 |
| Popis: | The therapeutic effect of anti-cancer monoclonal antibodies stems from their capacity to opsonize targeted cancer cells with subsequent phagocytic removal, induction of antibody-dependent cell-mediated cytotoxicity (ADCC) or induction of complement-mediated cytotoxicity (CDC). The major immune effector cells involved in these processes are natural killer (NK) cells and granulocytes. The latter and most prevalent blood cell population contributes to phagocytosis, but is not effective in inducing ADCC. Here, we report that targeted delivery of the tumoricidal protein tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to granulocyte marker C-type lectin-like molecule-1 (CLL1), using fusion protein CLL1:TRAIL, equips granulocytes with high levels of TRAIL. Upon CLL1-selective binding of this fusion protein, granulocytes acquire additional TRAIL-mediated cytotoxic activity that, importantly, potentiates antibody-mediated cytotoxicity of clinically used therapeutic antibodies (e.g., rituximab, cetuximab). Thus, CLL1:TRAIL could be used as an adjuvant to optimize the clinical potential of anticancer antibody therapy by augmenting tumoricidal activity of granulocytes. |
| Databáze: | OpenAIRE |
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