Tesis doctoral de Oihana Murillo Sauca
There is an ongoing explosion of knowledge in immunological sciences following the discovery of many agents that have the potential to serve as immunotherapeutic drugs. These agents include interleukin-15 (il-15) and agonistic anti-cd137 monoclonal antibodies (mabs). In animal models, both il-15 and anti-cd137 mabs have been shown to promote powerful anti-tumor responses capable of clearing established tumors, and they hold great expectations for cancer therapy in humans. However, for a rational design of treatments with these agents a fully understanding of the mechanisms behind their anti-tumor effects is needed. The driving force of the studies presented in this thesis has been the discovery of mechanistic aspects of il-15 and anti-cd137 mabs that could be suitable to improve cancer immunotherapy with these agents. In particular, our work has focused in three crucial points, to study: 1) the feasibility and mechanisms pertaining therapy of myeloma with anti-cd137 mabs, 2) the mechanisms of antigen presentation underlying immunotherapy with anti-cd137 mabs, and 3) the effects of hydrodynamically-delivered il-15 on nk cells and ikdcs, two immune cell subsets involved in tumor surveillance. This study demonstrates that anti-cd137 mab treatment shows benefit in various murine myeloma models and provides important clues on the involvement of cd8+ t lymphocytes and nk cells in the therapeutic immune response. In addition, our work provides evidence for an involvement of dc in the augmentation of anti-tumor ctl immunity by agonist anti-cd137 mabs; however the presence of dc is not absolutely required for the therapeutic effects of this anti-tumoral agent. Finally, this thesis proves the concept that liver gene transfer in mice provides a source of il-15 that thereby impacts the biology of ikdcs and nk cells up-regulating both their numbers and their cytolytic function.
Datos académicos de la tesis doctoral «Estudios de orientación terapéutica sobre la biología de la estimulación de cd137 y la transferencia génica de interleukina-15«
- Título de la tesis: Estudios de orientación terapéutica sobre la biología de la estimulación de cd137 y la transferencia génica de interleukina-15
- Autor: Oihana Murillo Sauca
- Universidad: Navarra
- Fecha de lectura de la tesis: 25/04/2008
Dirección y tribunal
- Director de la tesis
- Ignacio Javier Melero Bermejo
- Tribunal
- Presidente del tribunal: manuel Ortíz de landázuri busca
- José ignacio Mayordomo camara (vocal)
- pablo Villoslada diaz (vocal)
- Francisco Ruiz-cabello osuna (vocal)