DC Function CD137 Expression and Signaling

Dendritic cells acquire, internalize, process, and present antigens in the form of protease cleaved peptides derived from extracellular or intracellular antigens (Steinman, 1991). Processed peptides are then displayed in the context of MHC molecules on the cell surface and prime T cells bearing the appropriate peptide-specific TCR. The acquisition and presentation of antigens by dendritic cells is restricted to different stages of their development, the former function being carried out by...

CD137 as an Adjuvant for Adoptive T Cell Therapy and Bone Marrow Transplantation

Adoptive transfer of antigen specific T lymphocytes is certainly a promising strategy for cancer treatment (Dudley and Rosenberg, 2003), as well as for chronic or latent viral infections (Moss and Rickinson, 2005). Several approaches are possible which share in common the obtainment of autologous lymphocytes that are stimulated with antigen in vitro and then artificially expanded for infusion. In these treatments interleukin-2 is commonly coadministered to keep injected lymphocytes alive and...

CD137 Acting in Synergy with Cytokines and Other Costimulatory Molecules

Interleukin-12 as a recombinant protein has been one of the most promising anti-cancer agents arising from preclinical models. Unfortunately an underestimated maximal tolerated dose led to serious adverse effects in a phase II clinical trial that halted development. However systemic toxicity and local efficacy made IL-12 an excellent candidate for local gene therapy (Colombo and Trinchieri, 2002 Murphy et al., 2005). Tumor cell gene transfer of IL-12 has remarkable antitumor effects in mouse...

Effects of CD137 Engagement on CD8 T Cells in vivo

Ligation of CD137 on naive T cells by CD137L or CD137 antibody in the absence of TCR signal does not induce detectable responses DeBenedette et al., 1997 Pollok et al., 1993 . Because naive T cells do not express detectable CD137 Cannons etal., 2001 Pollok et al., 1995 , it is thus possible that TCR is required for upregulation of CD137 on T cell surface. Studies of CD137 expression in vitro indicate that CD137 is expressed 24 h after activation with peak expression at 48-72 h Cannons etal.,...

CD137 Ligand Activities on Monocytes and Macrophages

CD137 ligand is expressed constitutively on peripheral monocytes and mono-cyte macrophage cell lines Table 3.2 . The signal through CD137 ligand activates monocytes and the CD137 lig-and signal alone is sufficient for activation. When CD137 ligand is crosslinked by recombinant CD137 protein or an anti-CD137 ligand antibody, it induces adherence of monocytes within a few hours. The adherent monocytes change their shape over the course of a week and adopt the three basic macrophage morphologies,...