| Autor: |
Wang X; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA., Katayama A, Wang Y, Yu L, Favoino E, Sakakura K, Favole A, Tsuchikawa T, Silver S, Watkins SC, Kageshita T, Ferrone S |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer research [Cancer Res] 2011 Dec 15; Vol. 71 (24), pp. 7410-22. Date of Electronic Publication: 2011 Oct 21. |
| DOI: |
10.1158/0008-5472.CAN-10-1134 |
| Abstrakt: |
Cell surface chondroitin sulfate proteoglycan 4 (CSPG4) is an attractive target for antibody-based cancer immunotherapy because of its role in tumor cell biology, its high expression on malignant cells including cancer-initiating cells, and its restricted distribution in normal tissues. The clinical use of CSPG4 has been hampered by the lack of a CSPG4-specific chimeric, humanized, or fully human monoclonal antibody. To overcome this limitation, we generated a CSPG4-specific fully human single-chain antibody termed scFv-FcC21 and characterized its specificity and antitumor activity. Viable CSPG4(+) melanoma cells were used in a screen of a human scFv phage display library that included CDR3 engineered to optimize antibody binding sites. The scFv antibody isolated was then recombinantly engineered with a human immunoglobulin G1 Fc region to construct the fully human antibody scFv-FcC21, which recognized tumors of neuroectodermal origin, various types of carcinomas, mesotheliomas, and sarcomas as well as myeloid leukemias. scFv-FcC21 inhibited in vitro growth and migration of tumor cells and in vivo growth of human tumor xenografts. These effects were mediated by inhibition of the activation of extracellular signal-regulated kinase and focal adhesion kinase signaling pathways that are critical for tumor cell growth and migration, respectively. Our findings define the CSPG4-specific fully human scFv-FcC21 antibody as a candidate therapeutic agent to target the many types of tumors that express CSPG4. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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