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KREFTSATS-Særutlysning kreftmidler, historikk

Vaccination against B cell cancers: from experimental immunology to patients

Tildelt: kr 3,8 mill.

Aim: The goal is to improve the prognosis of patients with multiple myeloma and B cell lymphoma by vaccination with a recombinant antibody-like vaccine (Vaccibodies). Background: B cell tumors produce a highly tumor-specific antigen, monoclonal immunoglob ulin with unique variable(V) regions, that may be used for vaccination purposes. Vaccibodies: We have developed a novel vaccination strategy based on recombinant Ig-like molecules (Vaccibodies). Vaccibodies are dimeric molecules that express V regions fro m monoclonal Ig of a tumor, connected through a dimerization motif to another set of V regions that target antigen presenting cells (APC) for induction of powerful immune responses. Unpublished results: Vaccibodies have been genetically constructed. Vacci body proteins have a correct structure. Vaccibodies induce strong tumor-protective immune responses in mice, especially as a naked DNA vaccine. Experiments of the proposal: 1) Vaccibodies will be constructed and tested for a number of different mouse myel omas and B cell lymphomas. 2) The cellular mechanism of action of Vaccibodies will be investigated. 3) Vaccibodies will be constructed for human multiple myeloma and B cell lymphoma patients. 4) Vaccibodies of 3) (above) will be hybrid human/mouse molecul es that target mouse APC, and will be tested in mice. 5) We will construct hybrid Vaccibodies specific for targets on human APC (HLA-DP, CD14). 6) Fully human Vaccibodies will be produced and tested in HLA transgenic mice. 8) Fully human Vaccibodies will be used to vaccinate conventionally treated multiple myeloma and B cell lymphoma patients with minimal residual disease in clinical trials. Budget: Salaries for 2 researchers and expenditures total 1.25 million NOK/year. Project management: The project le ader, professor Bjarne Bogen MD, runs a 16-member lab at RH University Hospital. The translation to the clinic is performed in collaboration with Dr. Gedde-Dahl and Dr. Lauritzsen at RH and DNR University Hospitals.


KREFTSATS-Særutlysning kreftmidler, historikk