Development and characterization of recombinant human Fc:OX40L fusion protein linked via a coiled-coil trimerization domain.

ABSTRACT: OX40 (CD134) is a potent costimulatory molecule found on the surface of activated CD4(+) and CD8(+) T cells. Immunotherapy with OX40 agonists administered in vivo has demonstrated efficacy in several murine tumor models. A phase I clinical trial is currently underway in patients with advanced cancer using a mouse anti-CD134 monoclonal antibody. Therapy with this antibody will likely be limited to one cycle because patients develop neutralizing human anti-mouse antibody (HAMA). Therefore, we developed a humanized OX40 agonist that links the extracellular domain of human OX40L to the Fc domain of human IgG(1) via a trimerizing isoleucine zipper domain (ILZ). Physical characterization by velocity sedimentation revealed that this novel construct, hFcILZOX40L, was assembled into hexamers in whi

SUBMITTER: Morris NP 

PROVIDER: S-EPMC1950941 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature