George Georgiou Receives $1.7M Grant To Help The Immune System Eliminate Cancer Cells

Headshot of Professor George GeorgiouProfessor George Georgiou has received $1.7 million in funding from the Cancer Prevention and Research Institute of Texas (CPRIT) for the development of a therapeutic enzyme to help the body’s immune system eliminate cancer cells.

Certain cancer cells survive by keeping the immune system from recognizing and eliminating them through an immunosuppressive molecule called Kyn. Georgiou and his collaborators are developing a novel biologic drug for reversing the suppressive effects of Kyn on immune cells.

Kyn is produced when the amino acid Tryptophan is oxidized by one of three possible enzymes (i.e. IDO1, IDO2, TDO). Kyn is then transported outside the cell where it initiates ‘tumor tolerance’ by impeding the function of crucial cancer-fighting T cells.

Therapeutics developed to specifically reverse this kind of tumor-induced immune suppression (i.e. “immune checkpoint inhibitors”) are increasingly popular. In the case of Kyn, the primary strategy to date has been the development of small molecules to stop production of Kyn by inhibiting IDO1, IDO2, and TDO.

“While many small molecule drugs can be effective in treating various cancers, their application in the case of Kyn faces significant challenges,” said Georgiou. “To be successful, small molecules would have to inhibit IDO1, IDO2, and TDO simultaneously, which will complicate and likely hinder pharmaceutical development. Additionally, cancers are known to develop resistance to small molecule drugs as a whole.”

In an effort to overcome these problems, Georgiou ‘s approach uses an enzyme (Kynureninase) that degrades Kyn into safe byproducts and restores normal immune cell functions, resulting in dramatic growth retardation of mouse melanoma tumors. This therapeutic works to inhibit Kyn production regardless of which IDO/TDO enzyme may be expressed by a cancer cell, and it avoids the pitfalls of using small molecule Kyn inhibitors.

Georgiou’s team is working to expand upon this discovery and execute the product development and preclinical studies needed to deliver a powerful immune checkpoint inhibitor into the clinic for cancer therapy.

Read more about Georgiou who was recently named UT Inventor of the Year for his work to re-think cancer treatment.

CPRIT has awarded more than $1 billion in grants to Texas researchers, institutions, non-profits and private enterprises since beginning operations in 2009. Besides scientific research funding, CPRIT also provides funding for product development and prevention programs.



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