Download Executive Summary

New anti-CD24 monoclonal antibody-based therapy in active IBD (Ulcerative colitis and
Crohns' disease) patients
Inventors
Prof. Nadir Arber, Specialist in Gastroenterology, Head of the Integrated Cancer
Prevention Center, Tel Aviv Sourasky Medical Center
Background, highlights & our innovation:
The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are
chronic inflammatory disorders caused by dysregulated immune responses in genetically
predisposed individuals. IBD is characterized by oxidative stress, infiltration of inflammatory
cells and up-regulation of pro-inflammatory cytokines. Patients with long-standing IBD have an
increased risk of developing colorectal cancer (CRC) which is a major cause of morbidity and
mortality in the Western world. Many of the molecular alterations responsible for CRC, namely
chromosomal instability, hypermutability in oncogenes and tumor suppressor genes, play also a
role in colitis-associated colon carcinogenesis. CD24, a cell surface molecule, is a heavily
glycosilated phosphatidylinositol-anchored mucin-like protein that was shown to be a potential
oncogene in the multistep process of CRC carcinogenesis (Sagiv et al., 2006). CD24 is
overexpressed in a variety of malignancies including B-cell lymphomas, gliomas, small-cell and
non-small cell lung, hepatocellular, renal cell, nasopharyngeal, bladder, uterine, epithelial ovarian,
breast, prostate, and pancreatic carcinomas. Previous studies in our laboratory have shown an
increased expression of CD24 in colorectal adenomas and adenocarcinomas as compared to
normal adjacent tissue. Moreover, we found that treatment of human CRC (HT29) cells with antiCD24 monoclonal antibodies (mAbs) reduced their viability and inhibited cell growth in a timeand dose-dependent manner (Sagiv et al., 2008). This data suggests that CD24 is an important
target for chemoprevention and anti-tumor therapy.
We have evaluated the role of CD24 in IBD development in animal models of
experimental colitis induced by either DSS or TNBS in mice. Our data shows that treatment of
DSS or TNBS-induced colitis in mice, with anti-CD24 mAbs, induce a dose-dependent reduction
in the inflammation scores both at the macro- and microscopic levels (unpublished data). These
results suggest that CD24 is apparently involved in the development of IBD in mice. Therefore,
anti-CD24 antibody therapy is potentially useful for the treatment of colitis in mice and may be a
novel treatment for IBD in humans.
Potential applications:
Based on the fact that CD24 is overexpressed in CRC and plays a role in the multistep
process of CRC carcinogenesis we hypothesize that CD24 may play a role in the pathogenesis of
IBD and serve as a target for therapy of IBD using anti-CD24 mAb.