Blocking a Protein May Prevent Rejection

This finding was presented at the Basic Science Symposium of the Transplantation Society in Nantes (France) in June 2005.

In addition, due to its apparent tissue specificity, TZAP7 may act as a biomarker for diagnostic applications. These discoveries were made by GenPat77 (Berlin, Germany; www.genpat77.de), a company founded in 1998 and based on exclusively licensed intellectual property rights on immune-related targets from Brigham and Women's Hospital (Boston, MA, USA).

In recent studies, alloactivated primary human T cell lines were analyzed and an up-regulated cDNA fragment named TZAP7 was isolated and used to identify the full length clone from a human cDNA library. TZAP7 expression was then analyzed by northern and reverse-transcription-polymerase chain reaction (RT-PCR) analyses. Antisense inhibition experiments were performed to characterize the cellular response after suppression of TZAP7 signaling in human peripheral blood lymphocytes.

TZAP7 has been found to be up-regulated after 24 hours of alloactivation and exclusively expressed in lymph nodes, thymus, spleen, tonsils, and activated peripheral blood mononuclear cells. Blocking TZAP7 with antisense techniques resulted in a significant inhibition in the proliferation of mononuclear cells and a down regulation of CD25, CD28, CD71, and human leukocyte antigen (HLA) DR in T cells.

"This discovery of an entirely novel target is very exciting and demonstrates the broad applicability of our research,” observed Nalan Utku, CEO of GenPat77. "TZAP7 appears to play a key role in the Noch signaling pathway. These data suggest that blocking the action of this protein could lead to a more targeted approach to immune suppression, which is essential when treating disorders such as transplant rejection.”




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