Research Report 2010 - MDC

ant of CD3 delta coding for a 45-mer polypeptideappears to mediate the increase of the T-cell receptordensity. Characterization of this polypeptide and evaluationof its properties as an immunomodulatory agentis ongoing.Adoptive T-cell therapy for lymphomasTuan Duc Nguyen and Nina Schmolka in cooperation withT. Blankenstein and W. UckertHodgkin, Nasopharyngeal Carcinomas, and Post-TransplantLymphoproliferative Disorders (PTLD) are associatedwith Epstein-Barr Virus (EBV) infection. CD8 and CD4clones have been generated against EBV proteins. Thecorresponding TCRs have been cloned in expression vectorsfor generation of transgenic T cells for adoptivetherapy of EBV-associated diseases. Optimization ofTCR expression led to improved killing efficiency ofgene-modified T cells in vitro.Moreover, the B-cell antigens CD19 and CD22 areappealing targets for a transgenic T cell recognition.Generation of TCR vectors recognizing epitopes of theseantigens is being pursued in cooperation with Th.Blankenstein in a murine system with humanized TCRgene sequences.Development of less toxic immunotoxinstargeting CD22 positive lymphomasTuan Duc Nguyen, Oliver Schmetzer in cooperation withG. Moldenhauer (DKFZ)Immunoconjugates coupled to toxic agents havepotent biological activity but side effect that canseverely limit their use. In a new approach, our groupgenerates immunotoxins which are based on non-toxicsubstances like dithiocarbamate-based compounds orcatechins which has been isolated from green tea. Coupledto an Anti-CD22-antibody, which is rapidly internalizedfrom lymphoma cells, leads to apoptosis inductionin cancer cells.Selected PublicationsSchmetzer, O, Moldenhauer, G, Riesenberg, R, Pires, JR, Schlag, P, Pezzutto,A. (2005). Quality of recombinant protein determines the amount ofautoreactivity detected against the tumor-associated epithelial celladhesion molecule antigen: low frequency of antibodies against the naturalprotein. J Immunol. 174, 942-952.Sebelin-Wulf, K, Nguyen, TD, Oertel, S, Papp-Vary, M, Trappe, RU, Schulzki, A,Pezzutto, A, Riess, H, Subklewe, M. (2007). Quantitative analysis of EBVspecificCD4/CD8 T cell numbers, absolute CD4/CD8 T cell numbers andEBV load in solid organ transplant recipients with PLTD. Transpl Immunol.17, 203-210.Westermann, J, Nguyen-Hoai, T, Baldenhofer, G, Hopken, UE, Lipp, M,Dorken, B, Pezzutto, A. (2007). CCL19 (ELC) as an adjuvant for DNA vaccination:induction of a TH1-type T-cell response and enhancement of antitumorimmunity. Cancer Gene Ther. 14, 523-532.Westermann, J, Kopp, J, van Lessen, A, Hecker, AC, Baskaynak, G, Le Coutre,P, Dohner, K, Dohner, H, Dorken, B, Pezzutto, A. (2007). Vaccination withautologous non-irradiated dendritic cells in patients with bcr/abl+ chronicmyeloid leukaemia. Br J Haematol. 137, 297-306.Westermann J, Hecker AC, Flörcken A, Dörken B, Pezzutto A. Granulocytemacrophage-colony stimulating factor plus interleukin-2 plus alphainterferonplus 5-fluorouracil in the treatment of metastatic renal cellcancer: induction of CD80/86+ T cells indicates adverse outcome. JImmunother. 2009 Jul-Aug;32(6):667-75.Patent applicationsEpCAM MHC-Klasse-II bindende Peptide und davon abgeleitete Mutantenals Verstärker der zellulären tumorreaktiven immunantwort (MDC0506 EP)Peptides regulating the surface expression of the T cell receptorEuropean Patent Application EP1870420Cancer Research 131