Immunotherapy in multiple myeloma: Id-specific strategies suggested by studies in animal models
| Autor: | Bjarne Bogen, Alexandre Corthay, Marianne Frøyland, Zlatko Dembic, Katrin U. Lundin, Ludvig A. Munthe, Tobias Gedde-Dahl |
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| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Immunology CD1 Lymphocyte Activation Mice Antigen Immunoglobulin Idiotypes Antigens Neoplasm MHC class I Immunology and Allergy Cytotoxic T cell Animals Antigen-presenting cell CD40 biology Histocompatibility Antigens Class II Dendritic cell Dendritic Cells Disease Models Animal Oncology Monoclonal biology.protein Immunization Immunotherapy Multiple Myeloma |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0340-7004 |
| Popis: | Multiple myeloma (MM) cells produce monoclonal immunoglobulin (Ig) which serves as a truly tumor-specific antigen. The tumor-specific antigenic determinants are localized in the variable (V)-regions of the monoclonal Ig and are called idiotopes (Id). We review here the evidence obtained in a T-cell receptor (TCR) transgenic mouse model that Id-specific, MHC class II-restricted CD4+ T cells play a pivotal role in immunosurveillance and eradication of MHC class II-negative MM cells. In brief, monoclonal Ig secreted by MM cells is endocytosed and processed by antigen-presenting cells (APCs) in the tumor. Such tumor-resident dendritic cell APCs in turn present Id peptide on their class II molecules to Id-specific CD4+ T cells which become activated and indirectly kill the MHC class II-negative myeloma cells. However, if the Id-specific CD4+ cells fail to eliminate the MM cells during their initial encounter, the increasing number of tumor cells secretes so much monoclonal Ig that T-cell tolerance to Id is induced. Extending these findings to MM patients, Id-specific immunotherapy should be applied at a time of minimal residual disease and when new Id-specific T cells have been educated in the thymus, like after high-dose chemotherapy and autologous stem cell transplantation. |
| Databáze: | OpenAIRE |
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