CloneID: GBR500 (Vatelizumab, TMC-2206)
Antigen Long Description: The parental mouse antibody was generated by immunizing BALB/c mice with human fibrosarcoma HT1080 cells. The original humanized version was generated by grafting the CDRs of murine parental antibody onto human acceptor framework regions.
Buffer Composition: PBS only.
Uniprot Accession No.: P17301
Specificity Statement: This antibody binds an epitope in the domain I region of human α2 integrin. This epitope spans a region encompassing amino acid residues, K40, N73, Q89, Y93, R165, and N166 and optionally, other amino acid residues of the α2 integrin I domain. This antibody is also reported to cross react with cynomolgus monkey, rhesus macaque and rat α2 I domains. Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix.
Application Notes (Clone): The binding of this antibody to recombinant GST-human α2I domain fusion protein and intact α2β1 integrin was evaluated using ELISA. It was reported that this antibody bound immobilized human α2β1 integrin with a binding affinity in the nanomolar range. The reactivity of this antibody towards α2β1 integrin expressed on blood cells from different species was evaluated by flow cytometry (US7807794). In vitro, this antibody inhibits the binding of PC3 prostate cancer cells to collagen with an EC50 of 0.035 μg/ml. To study the impact of VLA-2 on extravasation in a PC3-luc metastasis model, this antibody was used to block VLA-2 before injection of tumor cells and by pre-dosing mice with a 50 mg/kg dose i.v. Bi-weekly treatment with this antibody at 5 mg/kg successfully slowed tumor growth and was as effective as bevacizumab 5 mg/kg treatment (Attinger et al., Cancer Research 2011). A study involving orthotopic mouse xenograft model used a DU145-luc cell line and explored the importance of VLA-2 for tumor growth in a physiological setting. It was reported that VLA-2 inhibition leads to modest growth reduction in subcutaneous xenografts (Hou et al., Mol Cancer Ther 2011). In a phase 2 clinical study in multiple sclerosis patients, the safety and efficacy of this antibody was evaluated. Following treatment with this antibody enhanced frequencies of regulatory T cells (TREG) were reported (PMID: 30783682).
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