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New target for cancer therapy identified, preclinical study shows
Date:1/31/2012

this relationship," said study lead investigator, Benoit J. Van den Eynde, M.D., Ph.D., Brussels Branch Director at LICR.

The group studied a series of 104 human tumor lines of different types to confirm the activity of TDO in tumor cells. They learned that 20 tumors expressed TDO only, 17 others expressed IDO1 only and 16 expressed both. The findings suggest that TDO and IDO1 enzymes represent complementary cancer immunotherapy targets, which if blocked could potentially impact 51% of all tumors.

Demonstrating TDO Expression and Its Role in Thwarting Immune Attack

Using a validated mouse tumor model, researchers established that TDO expression caused tumor cells to resist immune rejection. They first vaccinated the mice with an antigen that caused them to reject the tumor. Then they injected TDO-expressing tumor cells into the immunized mice. Researchers found that immunized mice no longer rejected the TDO-expressing tumors. This demonstrated that the presence of TDO prevented the immune system from attacking tumors.

In collaboration with scientists from the University of Namur (Belgium), the team then developed an active compound to inhibit TDO enzymatic activity. "Our study showed quite beautifully that the TDO inhibitor restored the ability of mice to reject tumors despite the presence of TDO in tumor cells," said Dr. Van den Eynde.

Research recently published in the October 6, 2011 issue of Nature (Opitz, C.A. et al.) validates today's study results by showing that TDO expression in human glioblastomas promotes tumor progression.

Toward Clinical Development of a TDO-inhibitor

The research team is moving forward to validate TDO inhibition in other preclinical models. Working closely with LICR colleagues in San Diego, the team will also conduct high-throughput screening to find a more stable TDO-inhibitor compound that can be advanced in clinical testing.

LICR plan
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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

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