Targeted Lymphoma Cell Death by Novel Signal Transduction Modifications.

摘要

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 No. 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.