Tim HuttenAllogenic stem cell transplantation is a potential curative therapy for hematological malignancies. However, many patients after therapy still relapse of their disease. Some potential causes for relapse are insufficient induction of tumor-reactive T cell and NK cell responses or dampening of anti-tumor immunity due to immune evasion by the tumor cells. To potentially gain more activated tumor-reactive T cells we created two different in vitro culture protocols to generate high amounts of different dendritic cells. These cells are capable to generate and activate tumor-reactive T cells in vitro as well as in vivo. Furthermore, we also show that we can potentially directly target dendritic cells in vivo to induce tumor-reactive T cell responses. Additionally, we investigated the inhibitory molecules expressed by tumor reactive T cells and tumor cells and inhibited this immune suppressive tumor microenvironment with blocking antibodies as well as on protein expression levels using siRNA.
In conclusion we used dendritic cells to induce more active tumor-reactive T cells and used blocking antibodies or siRNA manipulate the tumor microenvironment to be less immune-suppressive and thereby potentially prevent relapse in patients.
Date, time and location PhD defense Tim Hutten
- Date: 18 May 2018
- Time: 10:30 hrs
- Location: Radboud Universiteit, Academiezaal Aula, Comeniuslaan 2
Tim Hutten (1190) graduated in 2013 from Radboud university (master’s degree in Molecular Life Sciences). He carried out the above doctoral research at the department of laboratory of hematology (part of the department laboratory medicine) of the Radboud University Medical Center, within the Radboud institute for Molecular Life Sciences. Currently, he is the residency program in clinical chemistry at the department of Laboratory clinical chemistry and hematology of University Medical Center Utrecht.
- Promotor(s): Prof. Joop H. Jansen
- Co-promotor(s): Willemijn A. Hobo, PhD and Harry Dolstra, PhD