The use of IL-2 and other cytokines have been shown to be effective in the treatment of some types of cancer. However this treatment is significantly limited by the induction of severe toxic side effects. One significant side effect is the induction of capillary or vascular leak syndrome (VLS). The CD44 cell surface molecule has been shown to be directly involved in the induction of VLS. Recent studies suggest that the CD44 isoforms containing the v6 and/or v7 exons may plan an important role in a number of immunological processes. We hypothesize that the CD44 v6 and/or CD44 v7 isoforms play a direct role in IL-2-induced VLS. To test this hypothesis we will examine the influence of the CD44 v6 and CD44 v7 isoforms in the induction of VLS using the well established IL-2-induced VLS model. The successful completion of these experiments will provide important information as to the role of the v6 and v7 containing isoforms in the induction of VLS and give us some insight as to their normal role in the regulation of the immune response. In addition use of the mAb will provide information on the potential use of these antibodies in the prevention or treatment of IL-2- induced VLS.
| McKallip, Robert J; Fisher, Michael; Gunthert, Ursula et al. (2005) Role of CD44 and its v7 isoform in staphylococcal enterotoxin B-induced toxic shock: CD44 deficiency on hepatic mononuclear cells leads to reduced activation-induced apoptosis that results in increased liver damage. Infect Immun 73:50-61 |
| McKallip, Robert J; Fisher, Michael; Do, Yoonkyung et al. (2003) Targeted deletion of CD44v7 exon leads to decreased endothelial cell injury but not tumor cell killing mediated by interleukin-2-activated cytolytic lymphocytes. J Biol Chem 278:43818-30 |
| Mustafa, Amjad; McKallip, Robert J; Fisher, Michael et al. (2002) Regulation of interleukin-2-induced vascular leak syndrome by targeting CD44 using hyaluronic acid and anti-CD44 antibodies. J Immunother 25:476-88 |
| McKallip, Robert J; Do, Yoon; Fisher, Michael T et al. (2002) Role of CD44 in activation-induced cell death: CD44-deficient mice exhibit enhanced T cell response to conventional and superantigens. Int Immunol 14:1015-26 |
