Obsah

EpCAM-selective elimination of carcinoma cells by a novel MAP-based cytolytic fusion protein

Autor: Rainer Fischer, Manal Amoury, Wijnand Helfrich, Theo Thepen, Michael Huhn, Judith Niesen, Stefan Barth, Dmitrij Hristodorov, Anh-Tuan Pham, Nina Berges, Katharina Arens, Stefano Di Fiore, Radoslav Mladenov, Lea Hein
Přispěvatelé: Targeted Gynaecologic Oncology (TARGON), Translational Immunology Groningen (TRIGR), Publica
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Cancer Research
EP-CAM
medicine.medical_treatment
Cell
Apoptosis
chemistry.chemical_compound
Mice
Cancer immunotherapy
Tubulin
Neoplasms
PSEUDOMONAS EXOTOXIN
ADHESION MOLECULE
IN-VIVO
Mice
Inbred BALB C

Cell adhesion molecule
Epithelial cell adhesion molecule
respiratory system
Epithelial Cell Adhesion Molecule
medicine.anatomical_structure
Oncology
Female
Immunotherapy
VASCULAR LEAK SYNDROME
Protein Binding
CANCER-THERAPY
TUMOR-MODEL
Recombinant Fusion Proteins
Mice
Nude

tau Proteins
chemical and pharmacologic phenomena
Biology
Inhibitory Concentration 50
Open Reading Frames
Antigen
In vivo
Antigens
Neoplasm

Cell Line
Tumor

medicine
Animals
Humans
BREAST-CANCER
Cell Proliferation
Cell growth
Carcinoma
Fusion protein
Molecular biology
HEK293 Cells
IMMUNOTOXIN TREATMENT
chemistry
Cell Adhesion Molecules
HUMAN MONOCLONAL-ANTIBODY
Neoplasm Transplantation
Zdroj: Molecular cancer therapeutics, 13(9), 2194-2202. AMER ASSOC CANCER RESEARCH
ISSN: 1535-7163
Popis: In normal epithelia, the epithelial cell adhesion molecule (EpCAM) expression is relatively low and only present at the basolateral cell surface. In contrast, EpCAM is aberrantly overexpressed in various human carcinomas. Therefore, EpCAM is considered to be a highly promising target for antibody-based cancer immunotherapy. Here, we present a new and fully human cytolytic fusion protein (CFP), designated “anti–EpCAM(scFv)-MAP,” that is comprised of an EpCAM-specific antibody fragment (scFv) genetically fused to the microtubule-associated protein tau (MAP). Anti–EpCAM(scFv)-MAP shows potent EpCAM-restricted proapoptotic activity toward rapidly proliferating carcinoma cells. In vitro assays confirmed that treatment with anti–EpCAM(scFv)-MAP resulted in the colocalization and stabilization of microtubules, suggesting that this could be the potential mode of action. Dose-finding experiments indicated that anti–EpCAM(scFv)-MAP is well tolerated in mice. Using noninvasive far-red in vivo imaging in a tumor xenograft mouse model, we further demonstrated that anti–EpCAM(scFv)-MAP inhibited tumor growth in vivo. In conclusion, our data suggest that anti–EpCAM(scFv)-MAP may be of therapeutic value for the targeted elimination of EpCAM+ carcinomas. Mol Cancer Ther; 13(9); 2194–202. ©2014 AACR.
Databáze: OpenAIRE
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