Tesis doctoral de Lorea Beloki Bes
Adoptive transfer of cytomegalovirus (cmv)-specific t cells has shown promising results in preventing pathological effects caused by opportunistic cmv infection in patients following allogeneic hematopoietic stem cell transplantation. The majority of studies have used steady-state leukapheresis for cmv-reactive product manufacture, a collection obtained prior to or weeks after granulocyte-colony stimulating factor (g-csf) mobilization, but the procurement of this additional sample is often not available in the unrelated donor setting. If the cellular product for adoptive immunotherapy could be generated from the same g-csf mobilized collection, the problems associated with the additional harvest could be overcome. However, the tolerogenic effects induced by g-csf on t cells could affect the anti-viral in vivo functionality of cmv-specific t cells obtained from g-csf mobilized donor samples if they were infused into the patient. in this thesis it has been investigated the use of g-csf mobilized samples for the manufacture of cmv-specific t cells using two direct selection methods. First, cmv-specific t cells were isolated based on activation-dependent cd137 expression, which demonstrated a high specificity for cmv, the secretion of cytotoxic effector molecules, proliferation in response to the antigen and lysis of cmv-loaded target cells, showing that they shared the same characteristics as cmv-specific t cells obtained from non-mobilized cells. On the other hand, cmv-specific cd8+ t cells were isolated using mhc-multimers and showed that products obtained from g-csf mobilized samples were able to respond to the antigen by expressing activation markers and secreting pro-inflammatory cytokines and lytic molecules, but the in vitro proliferative capacity was impaired.
Datos académicos de la tesis doctoral «Evaluation and optimization of immunomagnetic methods for the purification and selection of cmv-specific cytotoxic t lymphocytes from g-csf primed peripheral blood mononuclear cells for adoptive immunotherapy«
- Título de la tesis: Evaluation and optimization of immunomagnetic methods for the purification and selection of cmv-specific cytotoxic t lymphocytes from g-csf primed peripheral blood mononuclear cells for adoptive immunotherapy
- Autor: Lorea Beloki Bes
- Universidad: Navarra
- Fecha de lectura de la tesis: 13/12/2014
Dirección y tribunal
- Director de la tesis
- arostegui Olavarria López
- Tribunal
- Presidente del tribunal: Juan josé Lasarte sagastibelza
- José alejandro Madrigal fernández (vocal)
- mercedes Rodriguez calvillo (vocal)
- aurelio Barricarte gurrea (vocal)