Anti-Integrin alpha.sub.v.beta.sub.3 mAbs [LM609](MABL-2157)

MABL-2157

crystallography, inhibition, IP, therapheutic, FC, IF, IHC

Engineer antibody

Human

LM609

Recombinant Antibody

The antibody specifically recognizes αVβ3 integrin. In particular, it recognizes an epitope on the αVβ3 integrin headpiece apex at the interface between the β-propeller and βI domains, sterically hindering access of large ligands to the RGD binding pocket.

αvβ3; αVβ3 integrin; alphav beta3 integrin; Vitronectin receptor; Vitronectin receptor subunit alpha; CD51; MED-523; Vitaxin; Etaracizumab; Abegrin

P06756

The original antibody was generated by immunizing BALB/c mice with purified cell adhesion receptor.

The antibody inhibited the attachment of human endothelial cells to fibrinogen, von Willebrand factor, and vitronectin (Cheresh et al, 1987; pmid:2442758). The antibody was used in FACS analysis on M21 cells. The antibody was used for immunoprecipitation analysis on M21 cells. The antibody is capable of preventing M21 cell attachment to vitronectin, von Willebrand factor, fibrinogen, and the Arg-Gly- Asp peptide (Cheresh et al, 1987; pmid:2447074). Flow cytometry analysis of integrin ανβ3 expression profiles of HUVEC was performed using this antibody. The antibody was used immunofluorescence against integrin ανβ3 (Diaz et al, 2020; pmid:31780581). The antibody was used in immunohistochemistry (Mena et al, 2014; pmid:24973039). The antibody blocked the binding of fibronectin and vitronectin proteins to ανβ3 in a solid-phase microtiter assay. In vitro studies demonstrated the antibody inhibits fibronectin binding to αVβ3 (Charo et al., 1990; pmid:1703545). The structure of the Fab fragment was determined using X-ray crystallography and the affinity between the antibody and the ectodomain of human ανβ3 integrin measured by surface plasmon resonance (Kd= 2.3*10^-8 M) (Borst et al., 2017; pmid:29033288). A fully humanized variant of the antibody MED-523 (Vitaxin) entered Phase I clinical trials for the treatment of cancers, resulting in no significant toxicity at any dose level (Gutheil et al., 2000; pmid:10955784). The second generation Etaracizumab (Abegrin) antibody, demonstrated increased binding affinity to αVβ3 with a significant reduction in brain tumor size following αVβ3-targeted radio-immunotherapy (Veeravagu et al., 2008; pmid:19010848).

Cheresh et al. Human endothelial cells synthesize and express an Arg-Gly- Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6471-5. PMID:2442758

The paper describes the generation and characterization of the antibody.

100 μg Purified antibody.

1 mg/ml.

Protein A affinity purified

PBS with 0.02% Proclin 300.

Store at 4⁰C for up to 3 months. For longer storage, aliquot and store at - 20⁰C.