Heterodimeric Bispecific Single-Chain Variable-Fragment Antibodies Against EpCAM and CD16 Induce Effective Antibody-Dependent Cellular Cytotoxicity Against Human Carcinoma Cells
| Autor: | Dan S. Kaufman, Seung Uk Oh, Michael R. Verneris, Daniel A. Vallera, Michelle K. Gleason, Bin Zhang, Jeffrey S. Miller, Valarie McCullar, Louis M. Weiner |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Cell Survival Recombinant Fusion Proteins Breast Neoplasms CD16 Cell Degranulation Interferon-gamma chemistry.chemical_compound Antigens Neoplasm Cell Line Tumor Neoplasms Antibodies Bispecific Humans Single-chain variable fragment Radiology Nuclear Medicine and imaging Pharmacology Antibody-dependent cell-mediated cytotoxicity Innate immune system biology Carcinoma Receptors IgG Degranulation Prostatic Neoplasms Epithelial cell adhesion molecule Original Articles General Medicine Epithelial Cell Adhesion Molecule Molecular biology Immunity Innate Killer Cells Natural Oncology chemistry Head and Neck Neoplasms Antibody Formation Colonic Neoplasms Cancer cell biology.protein Antibody Cell Adhesion Molecules Single-Chain Antibodies |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 28:274-282 |
| ISSN: | 1557-8852 1084-9785 |
| DOI: | 10.1089/cbr.2012.1329 |
| Popis: | A heterodimeric bispecific biological recombinant drug was synthesized by splicing DNA fragments from two fully humanized single-chain variable-fragment (scFV) antibody fragments forming a novel drug simultaneously recognizing the CD16 natural killer (NK) cell marker and the cancer marker epithelial cell adhesion molecule (EpCAM). The drug precipitously enhanced the killing of human carcinomas of the prostate, breast, colon, head, and neck even at very low effector:target ratios. The drug EpCAM16 rendered even nonactivated NK cell-proficient killers and activated them to kill via degranulation and cytokine production. Studies show that bispecific antibodies can be used to induce proficient killing of the carcinoma targets that ordinarily are resistant to NK-mediated killing. Apparently, the innate immune system can be effectively recruited to kill cancer cells using the bispecific antibody platform and EpCAM targeting. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|