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EBV
Generation of LCLs
Cell for Antigen expression
Packaging Cell Lines
What is EBV?
Immunology

EBV Technologies and Services


Epstein-Barr-Virus (EBV) is a member of the family herpesviruses. Almost anyone of us harbors the virus, normally without any clinical symptoms. EBV is the causative agent of infectious mononucleosis ("mono") and is also associated with different types of human cancer (nasopharyngeal carcinoma, Burkitt's lymphoma, Hodgkin disease). EBV is also a major cause of morbidity and mortality in immunocompromised hosts after solid organ and bone marrow transplantation. EBV is also the only known virus capable of infecting human B lymphocytes. Upon infection, these immune cells are immortalized by the virus and turned into powerful professional antigen presenting cells (APC).

B cell tropism and certain other biological features are unique to EBV and make the virus an interesting gene delivery system. However, due to the size of its genome, the virus has long been inaccessible to genetic manipulation. Only recently, a revolutionary genetic system, invented by the founders of Vaecgene, has made EBV a valuable tool for biomedicine. Today, Vaecgene is the only company in the world with the technical knowhow and exclusive licences to use EBV-derived plasmids for therapy. The first step to use EBV as a vector system was the establishment of a sytem that allows its genetic manipulation. Applying these newly established techniques and methods, we generated the first packaging cell line for herpesvirus vectors that can package DNA up to 180kb in size into a viral particle to transduce any gene(s) into B cells of normal or oncogenic human origin.

We offer to our customers the following services relying on our expertise in handling EBV and its derivatives:




Generation of EBV-immortalized human B Cell Lines (LCLs)
EBV-immortalized B cell lines (LCLs) are a valuable permanent source for almost unlimited amounts of DNA from almost any individual, like it is required for epidemiological and hereditary studies. Whenever desired, we can establish LCLs (or DNA isolated therefrom) from a small amount of peripheral blood derived from any donor.  In detail, we provide the following services:

• Generation of LCLs from any donor
• Isolation of cellular DNA from primary cells and LCLs
• Isolation and cryopreservation of plasma
• Quantification of EBV-infected cells

Please inquire for further information.






B cell Lines for Sustained Antigen Expression
EBV immortalized B cell lines (LCLs) are powerful antigen presenting cells. With respect to stimulation of specific T lymphocytes, they are comparable to dendritic cells (DCs). In contrast to DCs, they are of clonal origin and permanently available at almost infinite numbers. Our EBV technology allows immortalization of human B cells and simultaneous and sustained expression of distinct proteins like tumour antigens, cytokins, costimulatory molecules etc.

Simply incubate primary B-cells from any donor with our EBV supernatants and get immortalized B-cell lines presenting the protein of interest. So far, we have virus stocks available for EpCAM, pp65, HPV 6, 11, 16 (E6, E7, L1), her2/neu, IE1, B95.8 (control). Additionally, we offer custom cloning of your gene of interest into our immortalization/presentation vectors.

Please inquire for further information.





EBV packaging Cell Line
Human B cells (both primary cells and cell lines) are extremly recalcitrant to transfection by chemical or physical means. We rely on the natural tropism of Epstein Barr-Virus to transport plasmids with high efficiency into these cells. Based on the human cell line HEK293, we have generated the first (patent-protected) packaging system for Herpesviruses, that allows the production of recombinant infectious EBV particles. Packageable plasmids are:
mini-EBVs:
these plasmids carry all viral genes that are necessary for the immortalization of human B-cells, a feature that is unique to EBV. Introduce your gene of interest (GOI) onto a mini-EBV in order to generate  B cell lines that combine permanent growth with sustained expression of the GOI.

micro-EBVs:
contain all viral elements for packaging and CMV-driven expression of the GOI in human B cells. Contain hygromycin or neomycin resistance for selection.
Please inquire for further information.




Generation of Antigen specific human T Lymphocytes
MiniLCLs are mini-EBV infected antigen-presenting cell lines that efficiently induce specific T cell responses in vitro. Established easily from any donor, miniLCLs constitute a versatile system for the generation of large numbers of T cytotoxic lymphocytes for adoptive cell therapies. We have constructed mini-EBVs for the treatment of the following clinical conditions: Cell mediated immunity is an essential host factor in the control of most diseases, but cancer patients and patients receiving immunosuppression suffer from a defective immune system, unable to mount a tumour-specific immune response. Outside help may come in the form of adoptive transfer of specific T cells to establish immunity, which is an effective therapy for viral infections and malignancies
CMV Disease
CMV is a major clinical problem in immunocompromised patients and responsible for significant morbidity and mortality. Current treatment of CMV disease includes the administration of Gancyclovir and T cell preparations in vitro since adoptive therapy with such preparations may be of great clinical benefit.

Carcinoma, EBV-associated Lymphoma



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