title: A mouse model for immunotherapy of myeloma.
abstract: Myeloma cells secrete monoclonal immunoglobulin (Ig), called myeloma protein. The variable (V) regions of myeloma proteins are unique to each plasma cell tumor, and therefore contain highly tumor-specific antigenic determinants called idiotopes (Id). In ongoing clinical trials, myeloma patients are vaccinated against the Id of their own myeloma protein. T cells with specificity for Id are thought to be of importance in eradication of multiple myeloma. We have developed a mouse model to study the molecular and cellular mechanisms for how Id-specific T cell protect against myeloma. A T cell receptor (TCR) transgenic mouse model has been established. CD4+ T cells in these mice recognize a particular Id-peptide presented on a MHC class II molecule. The Id-peptide represents an 11-mere of the variable region L chain of a particular mouse myeloma, MOPC315. TCR-transgenic mice are protected against a challenge with MOPC315 cells. Id-specific CD4+ cells protect in the absence of anti-Id antibodies. Dendritic cells in s.c. tumors take up myeloma protein and present Id-peptide on class II molecules to CD4+ cells which become activated and then kill bystander myeloma cells by an unknown mechanism. When TCR-transgenic mice are injected with large amounts of MOPC315 myeloma cells, resistance is overcome and some 30% of mice develop tumors. In these mice, Id-specific T cells become deleted as the myeloma protein serum concentration exceeds 50 microg/ml. In conclusion, in an experimental model, Id-specific CD4+ T cells protect against myeloma. However, once a tumor is established, Id-specific T cells become incapacitated. Based on these results, it is suggested that Id-vaccination in humans should be reserved for eradication of minimal residual disease, eg after high dose chemotherapy and stem cell transplantation.
authors.affiliation: Institute of Immunology, Faculty of Medicine, University of Oslo, Rikshospitalet, Norway. b.bogen@labmed.uio.no
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes