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- Title
VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen.
- Authors
Nounamo, Bernice; Jousheghany, Fariba; Siegel, Eric Robb; Post, Steven R.; Kelly, Thomas; Ferrone, Soldano; Kieber-Emmons, Thomas; Monzavi-Karbassi, Behjatolah
- Abstract
The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. Therefore, the potential for off-tumor activity remains a serious concern when targeting CSPG4 therapeutically. Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. The functional assays demonstrated that VT68.2 inhibited cancer cell migration. These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides.
- Subjects
CHONDROITIN sulfate proteoglycan; MONOCLONAL antibodies; CARBOHYDRATES; TRIPLE-negative breast cancer; ANTIGENS; PEPTIDES; GLYCANS
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 3, p2506
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24032506