Adhesion molecules, mAbs

Anti-cytokine mAbs in rheumatoid arthritis 452 Anti-adhesion molecule mAbs 454 Anti-T cell mAbs in RA 455... 

Natalizumab (Tysabri ) is a recombinant humanized IgG4 mAb that binds to the a4-integrin subunit of a4(31 (VLA-4) and oA M (LPAM-1) integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the a4-mediated adhesion of leukocytes to their respective receptors.103 104 The receptor for a4pi, vascular cell adhesion molecule-1 (VCAM-1), is expressed on activated endothelial cells and is... 

Since adhesion molecules are of pivotal importance in cell trafficking and thus inflammation, they could constitute good therapeutic targets in RA. In fact, a murine mAb to intercellular adhesion molecule (ICAM)-l proved to lead to clinical improvement, (140) but repeated administration may have less effects, and the side-effect profile was also of major concern (141). Thus, anti-ICAM-1 may not be the strategy of choice. In this context it should be mentioned that TNFa blockade leads not only to clinical benefit but also to reduction of adhesion molecule expression. 

Bergese SD, Pelletier RP, Ohye RG, Vallera DA, Orosz CG. Treatment of mice with anti-CD3 mAb induces endothelial vascular cell adhesion molecule-1 expression. Transplantation 1994 57(5) 711-717. 

A large munber of mAbs targeting different mediators have been tested in RA. They inhibit either C3dokines, adhesion molecules, MHC, or T cells. 

Neuronal tracts can be labeled with the mAb 1D4 (DSHB 1 55-1 75, provided by Corey Goodman) directed against Fasciclin II (FasII), a membrane-bound adhesion molecule. The FasII landmark system in the ventral nerve cord (VNC) of the larva is originally described by Landgraf et al. [50] see also [51]. In the VNC, FasII-positive tracts provide a sort of 3D grid as they run... 

---