B-cell lymphoma idiotypes chimerized by gene targeting can induce tumor immunity
| Autor: | Jean-Pierre Kremer, Helge Menzel, Stefan Thierfelder, Ralph Mocikat, Michael Selmayr |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
Lymphoma B-Cell medicine.medical_treatment Gene Targeting Idiotype Immunoglobulin Heavy Chain Lymphoma Immunization Antigen presentation DNA vaccination Mice Immunoglobulin Idiotypes Tumor Cells Cultured Vaccines DNA medicine Animals Humans B-cell lymphoma Molecular Biology Mice Inbred BALB C Mice Inbred C3H biology Chimera Gene targeting Immunotherapy medicine.disease Adoptive Transfer Fusion protein Antibodies Anti-Idiotypic Immunization Immunology biology.protein Molecular Medicine Antibody Injections Intraperitoneal |
| Zdroj: | Cancer Gene Ther. 7, 501-506 (2000) |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/sj.cgt.7700129 |
| Popis: | Immunization with modified immunoglobulin (Ig) idiotypes (Ids) of B-cell lymphomas is an attractive approach of experimental tumor immunotherapy. We show here that B-lymphoma cells can be gene-modified by homologous recombination at the Ig heavy chain locus. Although it has been demonstrated previously that a protein vaccine containing a mouse/human chimeric Ig had no immunostimulatory effect, we show that a xenogeneic Fc segment attached to the Id by gene targeting in autologous murine tumor cells can serve as an immunogenic carrier and is capable of inducing tumor protection. A prerequisite for successful vaccination is the delivery of tumor cells that have been engineered to express the Id in the chimeric form rather than administration of the soluble chimeric protein. Also DNA vaccination with plasmids encoding chimeric Ids was reported to induce an anti-idiotypic response, suggesting that there might be related mechanisms such as enhanced antigen presentation. Immunization with engineered lymphoma cells is a very potent protocol: in the cell-based setting, minute levels of expression in the gene-targeted cells are sufficient to confer tumor immunity. Because the titers of anti-Id antibodies induced do not reflect the degree of tumor protection, the immune mechanisms responsible for tumor rejection cannot be ascribed exclusively to a humoral response. |
| Databáze: | OpenAIRE |
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