Functional Characterization of an scFv-Fc Antibody that Immunotherapeutically Targets the Common Cancer Cell Surface Proteoglycan CSPG4
Year: 2011
Type: article
Abstract: 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.
Source: Cancer Research
Authors: Xinhui Wang, Akihiro Katayama, Yangyang Wang, Ling Yu, Elvira Favoino, Koichi Sakakura, Alessandra Favole, Takahiro Tsuchikawa, Susan Silver, Simon C. Watkins, Toshiro Kageshita, Soldano Ferrone
Institutions: University of Pittsburgh, UPMC Hillman Cancer Center
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Antigen processing and HLA-peptide complexes in head and neck cancer, Combinatorial targeting of melanoma initiating cells, Rational Design of HMW-MAA Peptide Mimics, G571185835, Immune Escape in Human Cancer: Mechanisms and Therapeutic Implications, Invastigations on High Molecular Weight-Melanoma Associated Antigen as a target of the immunotherapy, Cancer Center Support Grant
OpenAlex ID: W2144814137