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This project is supported by the European Commission within the Fifth Framework Infrastructures program (contract no. QLRT-2000-01325, anticipated start date, 1st November 2001). See also the website of CORDIS - Community Research & Development Information Service of the EU (http://www.cordis.lu/en/home.html). ESTDAB is a continuation of the EUCAPS project (European Concerted Action on Peptide Sensitization (http://www.medizin.uni-tuebingen.de/eucaps/home/).
Members of the ESTDAB project:
ESTDAB will provide a service enabling investigators to search on-line for
HLA-typed, immunologically-characterised tumour cells available for distribution
from a central bank. This service will for the first time enable investigators
to identify cells possessing specific parameters important for studies of immunity,
immunogenetics, gene expression, metastasis, response to chemotherapy, and other
tumour biological experimentation. Cell lines, predominantly melanoma, will
be collected and characterised for the following parameters: HLA genotype and
surface expression of HLA molecules, expression of tumour antigens, antigen
processing capability, production of and response to cytokines and chemokines,
apoptosis regulation and expression of adhesion/accessory molecules.
A searchable data-base is being developed based on the current IMGT/HLA database
and will use modified tools already in existence for this database, to allow
for searching by single parameter, or clusters of parameters. This search program
will be made available on the Internet for use by any interested parties. Access
to the cells in the cell bank will, however, be restricted to bona fide investigators
after they have signed appropriate Material Transfer Agreements (MTAs) as provided
by the original donors of the lines. The service will be offered at nominal
cost to the user.
A central facility (CF) is established in the Center for Medical Research (ZMF)
of the University of Tübingen. Part of this consists of a cell bank currently
containing ca. 70 metastatic and primary melanoma cell lines collected from
European, Australian and US sources (see www.medizin.uni-tuebingen.de/eucaps/).
In the first stage of the project, this CF will continue to collect cell lines
and in addition, blood, fibroblast and melanoma samples will be collected from
patients entered into clinical immunotherapy trials. Cells will be cultured
in the CF, aliquotted and banked. In order to secure sufficient reserves, at
least 100 ampoules of each line will be frozen. Should this reserve ever be
in danger of becoming exhausted, cells will be thawed, propagated and again
frozen in batches of this size. Whenever this is required, all quality control
and the other tests will be repeated on the new frozen batch. Microbiological
and DNA fingerprinting quality control will be carried out on two representative
samples of each cell line before distribution to the other participants as frozen
samples on dry ice. Each partner will receive duplicate coded ampoules and return
data to the CF before the code is broken. Partner 2 (Danish Cancer Society,
Copenhagen) will assess expression of known tumour antigens, Partner 3 (Karolinska
Institute, Stockholm) will study cytokine production and response, and antigen
processing, Partners 4 & 5 (Anthony Nolan Bone Marrow Trust, London; University
Hospital, Granada) will perform HLA typing. In addition, the coordinator´s
lab will carry out surface marker phenotyping by FACS analysis and also assess
apoptosis control including expression of fas, fas-ligand, FAP-1, DR3, FLICE
etc., which critically impact upon the tumour cell lines´ biological and
immunological behaviour. Partner 5 will also help to assess expression of apoptosis-control
molecules. Should the distributed hidden duplicate samples yield disparate results,
the respective partner will be required to clarify the data. In this way, an
extensive characterisation of the lines will be achieved in a standardised,
quality-controlled fashion. Once this is accomplished, each cell line will be
added to the data base and a small number of ampoules of each cell line sent
for replicate storage to at least one of the partners, so that the CF is not
the only center with the core cell bank. The lines will be made available from
the CF to interested investigators, through modified interactive search programs
originally developed by Partner 4 for bone marrow donor selection. Tools for
matching sets of desired criteria to available cell lines will for the first
time enable investigators to locate tumour cell lines (and in many instances,
matching B-LCL, as well in some cases other tissues, such as fibroblasts) with
the characteristic pattern of expressed molecules appropriate to their experimental
needs.
Graham Pawelec Tel. +49 7071 2982805 Fax +49 7071 295567 E-mail: graham.pawelec@uni-tuebingen.de |
Section for Transplantation Immunology and Immunohaematology
Zentrum für Medizinische Forschung Waldhörnlestr. 22 D-72072 Tübingen Federal Republic of Germany |
Last updated 06 April 2002. Sitemasters: mathias.diane.blaurock@t-online.de