Future plans - development of new diagnostic and therapeutic tools

 

 
Vaccine studies in lymphomas under planning

Dendritic tumor cell vaccinations on malignant lymphoma undergoing allogeneic transplantation with reduced conditioning.
Establishing allogeneic stem cell transplants with reduced conditioning at DNR/RH as part of a NIH protol will be the first step to develop more advanced studies during the next 2-3 years. We have made plans to apply the know-how at our institution for transfection of tumour cell RNA into dendritic cells be electroporation, to vaccinate lymphoma patients post-transplant in order to generate T-cell responses against the patients lymphoma cells and hopefully prevent relapse.

Vaccibodies
In collaboration with professor Bjarne Bogen, Rikshospitalet, Oslo we are starting a project aiming to elicit immune responses in patients with indolent, follicular B-cell lymphomas. The project is studying responses to a newly developed vaccine formulation called Vaccibodies, which are partly made of the proteins or of the genes coding for the variable fragment of the immunoglobulin molecule of the malignant B cells. The study is on a preclinical level, but we intend to create data which hopefully will form the basis of a phase I study where patients with indolent, follicular lymphomas in complete remission induced by chemotherapy will undergo vaccination with Vaccibodies made from their own tumor immunoglobulin molecules.

Development of novel diagnostic tools

Development of a diagnostic lymphoma microarray
We are currently, through the LLMPP collaboration, developing a diagnostic microarray with 500-1000 genes, which are selected from the various studies of the main subgroups of B cell lymphomas. The array has been initially tested and looks very promising, giving similar prediction of subgroups and prognostic information similar to those obtained in parallel studies using the Lymphochip cDNA arrays. The translational pathological research verifying the diagnostic accuracy and robustness will be performed in a large collaborative study involving our hospital. Hopefully, this diagnostic array eventually can be used for routine diagnostic profiling and evaluation of therapeutic responses. It is conceivable that smaller chips with fewer and selected genes will be used for each tumor entity.

Identification of clinically relevant T-cell lymphoma entities: the international peripheral T/NK cell lymphoma project
A biologically meaningful classification of lymphoma is the absolute basis of any successful future treatment of the disease. The classification of B-cell lymphomas based on histologic, immunophenotypic, genetic and clinical data has been clinically validated in a large international study conducted by the renown lymphoma oncologist, James Armitage (University of Nebraska Medical Center) and has eventually allowed to establish the WHO criteria that are now universally used. Such study has as yet not been conducted for the classification of T-cell lymphomas based on the same principles. Therefore, a new world-wide study conducted by James Armitage has now been established of which the pathologists and clinicians of our centre, one of the handful of participating European groups, are active participants.

Other diagnostic tools
Probes or antibodies against gene and gene products that are primarily expressed in B-lymphocytes or mutated in B-cell lymphomas, will be potential candidates as new diagnostic tools. For previously unknown genes it will be important to perform a detailed study of the expression pattern in normal tissues, including different subpopulations of B-lymphocytes, as well as in various subtypes of malignant B-cell lymphomas to examine if such genes can represent new markers of diagnostic interest. Unique genes with potential diagnostic importance will be provide a basis for specific diagnostics in the form of PCR kits and other gene tests, and monoclonal antibodies for diagnostic use will be produced against the corresponding recombinant protein or selected synthetic peptides.

More   May 12, 2004