Targeted Lymphoma Cell Death by Novel Signal Transduction Modifications
Abstract
The proposed research set to; 1) create and characterize CD22-binding peptides that initiate signal transduction and apoptosis in non-Hodgkin s lymphoma (NHL), 2) optimize CD22-mediated signal transduction and lymphomacidal properties of ligand blocking anti-CD22 monoclonal antibodies (mAbs) and peptides with CD22-specific phosphatase inhibition and 3) correlate mAb-mediated and anti-CD22 peptide-mediated in vivo physiologic changes, efficacy, and tumor targeting using advanced immuno-positron emission topography (i-PET) and FDG-PET imaging technology. Since funding we have identified five peptides that are based on CDR s of anti-CD22 mAbs. Peptide 5 has been characterized and described in the annual report for year 1 and 2. Because peptide 5 was not target specific it could not be developed further. We then created reagents in year 3 to optimize targeting (CD22 + epithelial cell line and a new combinatorial peptide library). Within year 4 we identified addition peptides that one of which was B cell and CD22 specific (peptide #8). This peptide was found to induce effective cell killing in the lymphoma cell line, Ramos. We have now begun to characterize the specificity, signaling, cytotoxic and apoptotic potential.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2011
- Accession Number
- ADA566413
Entities
People
- Joseph Tuscano
Organizations
- University of California