Immunotherapy is a promising novel strategy for cancer therapy. It consists of the therapeutic vaccination of cancer patients to stimulate their (natural) immune system against cancer cells. This approach, however, showed limited efficacy in vivo. Cancer cells are actually able to develop enzymatic mechanisms allowing tumours to resist or escape the immune rejection. Among the enzymes involved, the indoleamine 2,3-dioxygenases IDO and TDO represents potential actors.[1-3] These enzymes catalyse the rapid degradation of tryptophan (Trp) through the kynurenine (KYN) pathway to form quinolinic acid (QA). This results in a local Trp depletion that severely affects the proliferation of T lymphocytes and is thereby profoundly immunosuppressive.
This project was funded in part by Télévie (FNRS grant 7.4.543.07) and led in collaboration with the team of Pr Benoit Van Den Eynde (LICR, UCL) and Pr Moreno Galeni (CIP, ULG) aims at developing novel TDO inhibitors using a rational approach. These inhibitors will allow a better understanding of the role of TDO in the phenomenon of immunosuppression, especially in cancerous tumors.
From a certain synthesized inhibitors, crystallographic structure was obtained and linking with a docking study of these inhibitors in a model of TDO Ralstonia metallidurans (rmTDO) humanized. Furthermore, in parallel with this study, these compounds have been tested on the enzyme overexpressed and purified previously in order to better understand how to interact with inhibitors TDO. This process is presented on this poster.
|Pages||Abstracts, The sixth Belgian Crystallography Symposium (BCS-6), 13 October 2010, Brussels, Belgium|
|Number of pages||1|
|Publication status||Published - 2010|
|Event||The sixth Belgian Crystallography Symposium (BCS-6) - Brussels, Belgium|
Duration: 13 Oct 2010 → …
|Symposium||The sixth Belgian Crystallography Symposium (BCS-6)|
|Period||13/10/10 → …|