Accession Number : ADA566413


Title :   Targeted Lymphoma Cell Death by Novel Signal Transduction Modifications


Descriptive Note : Final rept. 15 Jun 2007-14 Jun 2011


Corporate Author : CALIFORNIA UNIV DAVIS


Personal Author(s) : Tuscano, Joseph


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a566413.pdf


Report Date : Jul 2011


Pagination or Media Count : 33


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.


Descriptors :   *LYMPHOMAS , *PEPTIDES , APOPTOSIS , B LYMPHOCYTES , CELLS(BIOLOGY) , CHEMICAL AGENTS , CYTOTOXINS , DEATH , EPITHELIUM , NEOPLASMS , TOPOGRAPHY


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research
      Toxicology


Distribution Statement : APPROVED FOR PUBLIC RELEASE