Optimization of dendritic cell vaccines for cancer therapy: interleukin-15 transpresentation and in situ immune checkpoint inhibition

Datum: 14 juni 2017

Locatie: Campus Drie Eiken, Building O, room O.5 - Universiteitsplein 1 - 2610 WILRIJK (route: UAntwerpen, Campus Drie Eiken)

Tijdstip: 17 uur

Promovendus: Johan Van den Bergh

Promotor: Prof E. Smits & Prof V. Van Tendeloo

Korte beschrijving: PhD defence Johan Van den Bergh - Faculty of Medicine and Health Sciences



Abstract

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Despite major medical advances, AML still has a poor prognosis with a five-year survival rate of less than 26%. Although the majority of patients reach complete remission after the standard treatment, the majority of patients relapses within two years due to the presence of residual tumor cells. Therefore, there is a clear need for new effective therapies that can destroy the remaining malignant AML (stem) cells. At present, there is much interest in the use of dendritic cell (DC)-based vaccination, as this cell therapy is capable of mobilizing the patient's own immune system, resulting in the in vivo generation of an antitumor response without serious toxicity or side effects. However, clinical effectiveness of DC vaccines needs to be further improved. In this context, redirecting the balance between immune-activating and -inhibitory signals of DC could improve the antitumor functions of immune cells, such as natural killer (NK) cells and CD8+ T cells, which are the main killer cells of the immune system. Two of the most promising immune modulators involved in the new era of cancer therapy are interleukin (IL)-15, as immune-stimulatory agent, and the programmed death ligands (PD-L) 1 and 2, as immune-inhibitory checkpoints. By introducing IL-15 in DC and/or by suppressing PD-L on the DC membrane, this study aims to increase both their NK cell- and T cell-stimulatory properties. This hypothesis is based on the fact that both immune cell types express the IL-15 receptor (IL-15R) moieties responsible for IL-15 signaling and the PD-1 receptor which can interact both with its ligands PD-L1 and PD-L2.



Inkomprijs: free

Url: https://www.uantwerpen.be/nl/faculteiten/geneeskunde-gezondheidswetenschappen/