Crohn’s Disease (CD) is a chronic relapsing/remitting inflammatory disease of the gastrointestinal tract affecting about 800,000 patients in the US and Europe alone with rising incidence rates. In addition to reduced quality of life for CD patients, the chronic inflammation associated with CD ultimately leads to neoplasia, strictures, abscesses, and fistulas often requiring multiple surgical interventions. Current standard of care include steroids, immunomodulators, and anti-TNF-alpha therapy. However, 15-20% of patients are refractory to standard of care. Additionally, therapeutic interventions such as anti-TNF-alpha carry significant side effects including neoplastic events and reactivation of latent TB infections.
Drs. Giulia Roda and Lloyd Mayer have shown that CD8+ T-regulatory cells (Tregs) isolated from CD patients have reduced immunosuppressive activity and this reduced immunosuppressive activity may be partially causative of the inflammatory phenotype seen in CD patients. The loss of Treg activity in CD results from reduced expression of CEACAM5, a critical mediator of Treg activation. Using a peptide scanning approach, Drs. Roda and Mayer identified critical peptides of CEACAM5 that are able to activate Treg activity in CD patient-derived samples and reduce the inflammatory activity of CD4+ T cells in ex vivo patient-derived cellular assays. Such peptides have the potential to successfully treat the inflammatory phenotype seen in CD.
Current Development Status
- Initial validation of immunotherapeutic potential of peptides in ex vivo patient derived cellular assays
- Refined peptide library to identify optimal therapeutic peptide
- Additional validation studies underway using patient-derived samples
- Initial administration, PK, and toxicology studies planned in mice
Applications
- Crohn’s Disease
Advantages
- Restores physiologic immune response to inflammation which may reduce side effect profile compared to current therapeutic approaches
- Small peptide allows for better administration and distribution profile compared to large molecule approaches
Publications
- Roda, G. “CEACAM5 Small Peptides Restore the Suppressive Activity of Lamina Propria CD8+ T Cells in Crohn’s Disease.” Digestive Diseases Week Oral Presentation. May 3-6, Chicago Illinois
- Roda, G. Manuscript in preparation
Patent Status
- International Application PCT/US2015/028864 filed May 1, 2015
- Status: Pending
Contact
Lisa Placanica, Ph.D., CLP
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7325