Researchers at The University of Texas at Austin have developed a new approach to treating cancer using enzyme therapy.
The enzyme, PEG-KYNase, does not directly kill cancer cells but instead empowers the immune system to eradicate unwanted cells on its own. PEG-KYNase is designed to degrade kynurenine, a metabolite produced by numerous tumors that suppresses the immune system. The UT team’s findings were published in a recent issue of Nature Biotechnology.
A healthy, fully functioning immune system can combat the spread of cancer cells and eliminate tumors by itself. However, tumors have evolved in multiple ways to suppress the immune system, leading to the growth and metastasis of cancer cells… Continue reading.
A research team led by Texas ChE Professor George Georgiou has engineered an enzyme that safely treats prostate and breast cancer in animals and also lengthens the lifespan of models that develop chronic lymphocytic leukemia. The new treatment and results from preclinical trials are described in a paper published in the Nov. 21 issue of Nature Medicine.
Many cancers depend on the non-essential amino acid cysteine to grow, survive, and even resist many chemotherapeutics. Georgiou, a professor of molecular biosciences and chemical engineering, and Everett Stone, a research assistant professor in molecular biosciences, led a team that was able to capitalize upon these observations by engineering a human enzyme to systemically degrade cysteine. The UT research team showed that injection of their cysteine-degrading enzyme into animals leads to the elimination of cysteine in blood and thus deprives the tumor cells of what they need to grow.
“With this treatment approach, cancers build up toxic molecules of their own making because we took away their ability to make an antioxidant that is really important to them—but not necessarily important to a normal cell,” Stone says. “A very important component of our result is that there are no apparent side effects.”
Cysteine is considered a non-essential amino acid in healthy cells because it is produced by most tissues and does not have to be taken up in the diet. It plays a central role in the defense of cells against oxidation. Numerous tumors are known to be oxidatively stressed, in part because of their fast growth; for this reason, they require cysteine, which they take up from blood.
Researchers at The University of Texas at Austin, including Texas ChE’s Dr. George Georgiou and Dr. Jennifer Maynard, successfully culminated years of work when a drug they engineered for the treatment and prevention of inhalational anthrax — the anthrax antitoxin obiltoxaximab — received approval March 21 from the U.S. Food and Drug Administration (FDA). Part of the molecule was engineered at UT Austin before being licensed to New Jersey-based pharmaceutical company Elusys Therapeutics for further development. It will be sold under the name Anthim.
The university researchers, whose work began more than a decade ago, engineered a high-affinity, “sticky” antibody fragment that binds to the anthrax toxin, blocking its activity.
On March 21, the FDA approved Anthim (obiltoxaximab) to treat inhalational anthrax in combination with appropriate antibacterial drugs and to prevent the disease when alternative therapies are not available or appropriate.
Texas ChE professor George Georgiou, the Laura Jennings Turner Chair in Engineering, has been named a Fellow of the National Academy of Inventors (NAI).
Election to NAI fellow status is a “professional distinction given to renowned academic inventors who have demonstrated a prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on quality of life, economic development and the welfare of society,” according to the academy.
Georgiou is being recognized for his work on the discovery and preclinical development of antibody and enzyme therapeutics, the development of tools for the understanding of serological and B cell antibody repertoire and on the high-resolution evaluation of humoral responses to vaccines for seasonal influenza and other diseases. In addition to teaching chemical engineering, he is also a professor in the University of Texas at Austin’s Biomedical Engineering Department and Department of Molecular Biosciences in the College of Natural Sciences.
The American Academy of Arts and Sciences announced the election of new members this week, including biochemist and chemical engineering professor George Georgiou.
Georgiou has been recognized for paving the way for advances in medicine that improve people’s lives, with discoveries such as a technology that has been incorporated into drugs that fight macular degeneration and osteoporosis.
“We are tremendously proud of George for his election into AAAS,” said Sharon L. Wood, dean of the Cockrell School of Engineering. “He is a pioneer in the fields of protein engineering and therapeutics, and the technologies he has developed are changing the lives of patients around the world.”
Professor 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.
George Georgiou, professor of chemical and biomedical engineering at The University of Texas at Austin, has been named Inventor of the Year by the university’s Office of Technology Commercialization.
The award recognizes Georgiou for commercializing industry-changing technologies, preparing students to follow in his footsteps and proving that What Starts Here Changes the World.
In 2013, Nature Biotechnology named Georgiou one of the world’s top 20 translational researchers, and his far-reaching body of work backs up that honor. With 29 issued U.S. patents and 46 patent applications, Georgiou has proven to be one of the most prolific inventors at UT Austin. What uniquely qualifies him as Inventor of the Year is the societal and commercial importance of his developed technologies. His inventions account for 15 distinct technologies, and more than 50 percent of his 75 issued and pending patents have been licensed or optioned to pharmaceutical or biotechnology companies. By comparison, only about 5 percent of patent applications from academic institutions are licensed.
“George is an amazing person, and he really straddles the fence between doing great basic science and great applied science,” says Everett Stone, a research scientist who works with Georgiou. “He’s an engineer by background, but he delves into every area. He’s not afraid to change direction — he just goes for it. The work over his career spans hundreds of different avenues, and he’s been highly successful in all of them.”
Nature Biotechnology ranked George Georgiou, a professor in the Cockrell School of Engineering, one of the world’s top 20 translational researchers in 2013.
Georgiou, a renowned biomedical engineer and molecular biologist, is a leading authority in the discovery, development and manufacturing of protein therapeutics. Nature Biotechnology recognized Georgiou for his output of U.S. and European patents issued and papers of translational interest published.
Over his 28-year career, Georgiou has been one of the most active researchers at The University of Texas at Austin. He is co-inventor of a total of 29 U.S. patents and 46 U.S. patent applications (38 published and eight pending). According to Georgiou, 14 patent suites, each comprising multiple patents, have been licensed to 17 biotechnology or pharmaceutical companies.
At UT Austin, Georgiou’s laboratory has developed methods for the discovery, manufacturing and use of therapeutic proteins, and also discovered several protein drugs currently in clinical development.