Anti-CXCL12 [30D8]

Absolute Antibody

Anti-CXCL12 [30D8]

9

This antibody is specific for CXCL12. In mouse and human, it has been shown to bind CXCL12alpha, CXCL12beta, and CXCL12gamma.

The original format of this antibody (Hamster IgG, kappa) completely blocked chemotaxis of Jurkat cells elicited by CXCL12alpha with an average IC50 of approximately 0.5 microg/mL (~3 nmol/L). This antibody successfully and specifically blocked CXCL12alpha binding to CXCR4 and CXCR7, inhibited CXCL12alpha-induced Rac1 activation in a dose-dependent manner, and effectively suppressed primary tumor growth in mouse lymphoma and Lewis lung carcinoma models. Additionally, 30D8 showed significant inhibition of lung metastasis in a breast cancer model and reduced choroidal neovascularization in a mouse model. In a collagen-induced arthritis mouse model, 30D8 slowed down disease progression and, in combination with anti-TNF antibody, prevented disease advancement, reducing bone-erosive changes. The humanized version of this antibody (hu30D8) demonstrated binding affinity not only to CXCL12alpha but also to CXCL12beta and CXCL12gamma in direct ELISA assays. It effectively blocked CXCL12alpha- and CXCL12beta-induced migration of Jurkat cells, displaying an IC50 of 0.16 microg/mL (~1 nmol/L), comparable to its hamster and mouse/hamster chimeric counterparts. Although the exact affinity for binding to hu30D8 could not be reliably determined due to technical limitations, the dissociation constant (KD) was measured as 0.923 and 2.39 nmol/L for human and mouse CXCL12, respectively, using Biolayer Interferometry. The crystal structure of hu30D8 Fab in complex with human CXCL12alpha was determined. The pharmacokinetic characteristics of 30D8 and hu30D8 were extensively studied. Both formats displayed rapid clearance following administration, with distinct behaviors in different animal models. 30D8, administered intraperitoneally, exhibited fast clearance in mice yet showed no significant accumulation during prolonged dosing, suggesting consistent clearance over time. Hu30D8, when given intravenously, exhibited rapid clearance in mice but had normal clearance in rats, indicating species-specific differences. Various mutations and epitope interactions were explored: hu30D8D95A, which disrupted a crucial interaction, exhibited significantly slower clearance, emphasizing the impact of epitope interactions on clearance rates (Zhong et al., 2013; PMID: 23812669). The humanized version of this antibody is available on request. Please contact us if interested.

ELISA, Neutralisation/Blocking, Other Application

Research Use Only

Monoclonal

30D8

Mouse

IgG2a

This is a reformatted mouse IgG2a Fc Silent™ antibody, based on the original mouse IgG format, created for improved compatibility with existing reagents, assays and techniques.

Human, Monkey, Mouse, Rat

-20°C,2°C to 8°C

12352203