Zsolt Sebestyén

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The interaction of the cell surface proteins plays a key role in the process of transmembrane signaling. Receptor clustering and changes in their conformation are often essential factors in the final outcome of ligand receptor interactions. Fluorescence resonance energy transfer (FRET) is an excellent tool for determining distance relationships and(More)
The ErbB family of transmembrane receptor tyrosine kinases plays an important role in the pathogenesis of many cancers. The four members of the family, ErbB1-4, form various homo- and heterodimers during the course of signal transduction. A second hierarchical level of molecular associations involving 10(2)-10(3) molecules, termed large-scale clustering,(More)
TCR gene therapy is adversely affected by newly formed TCRalphabeta heterodimers comprising exogenous and endogenous TCR chains that dilute expression of transgenic TCRalphabeta dimers and are potentially self-reactive. We have addressed TCR mispairing by using a modified two-chain TCR that encompasses total human CD3zeta with specificities for three(More)
Adoptive transfer of T cells that are gene engineered to express a defined TCR represents a feasible and promising therapy for patients with tumors. However, TCR gene therapy is hindered by the transient presence and effectiveness of transferred T cells, which are anticipated to be improved by adequate T cell costimulation. In this article, we report the(More)
To improve safety and specificity of oncolytic adenoviruses, we introduced T-cell receptors (TCR) specific for a unique class of truly tumor-specific antigens into the adenoviral fiber protein. The adenoviral fiber knob responsible for attachment to the coxsackie-adenoviral receptor (CAR) on target cells was replaced by a single-chain TCR (scTCR) molecule(More)
Allogeneic stem cell transplantation (allo-SCT) has so far been the most effective immunotherapy for hematological malignancies. However, it is becoming increasingly clear that the immunotherapeutic concepts underlying allo-SCT as well as the traditional dissection of the immune system into innate and adaptive arms need substantial refinement. More and more(More)
Human cytomegalovirus (CMV) infections and relapse of disease remain major problems after allogeneic stem cell transplantation (allo-SCT), in particular in combination with CMV-negative donors or cordblood transplantations. Recent data suggest a paradoxical association between CMV reactivation after allo-SCT and reduced leukemic relapse. Given the potential(More)
ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2 association patterns involving integrins and lipid rafts. Flow cytometric FRET and confocal microscopic measurements revealed(More)
An investigation into the role of CD45 isoforms in T cell antigen receptor signal transduction was carried out by transfecting CD45-negative CD4(+)CD8(+) HPB-ALL T cells with the CD45R0, CD45RBC, and CD45RABC isoforms. Fluorescence resonance energy transfer analysis showed that the CD45R0 isoform, but not the CD45RBC or CD45RABC isoforms, was found as(More)
T cell receptor (TCR) gene therapy provides patients with autologous T cells that are genetically engineered with TCRalphabeta chains and constitutes a promising approach for the treatment of tumors and virus infections. Among the current challenges of TCR gene therapy is the optimization of TCRalpha and beta transgene pairing to enhance the functional(More)