ChBE Seminar Series - 3:30 p.m. EDT March 23 - George Georgiou (Virtual)

Wed Mar 23 3:30 pm to 4:30 pm
Virtual Link

George GeorgiouGeorge Georgiou, Professor, Departments of Chemical Engineering, Molecular Biosciences, Biomedical Engineering,
and Oncology, University of Texas, Austin

"Engineering Enzyme Therapeutics for Cancer Immunotherapy and Inborn Errors of Metabolism"

 

Virtual Link: https://gatech.zoom.us/j/94954036977?pwd=TUw0WVFYMnFaZ3ZVSmlvcDZzaUE0QT09

Password = ChBE2022

Abstract:

Cancer is predicated on the suppression of adaptive immune responses.   A key mechanism for immune escape in cancer arises from genetic changes and/or metabolic re-programming that result in the aberrant accumulation of metabolites that potently suppress lymphocyte function.   Our lab has pioneered the concept of immune check-point enzyme therapy whereby systemic administration of pharmacologically optimized, human engineered enzymes is employed to activate the immune system leading to cancer eradication.    We have invented and led the development of 5 such engineered enzymes that are now either in clinical or late-stage preclinical evaluation.  In this presentation I will describe the mechanism of action for two of these checkpoint enzymes and the respective protein engineering campaigns that led to the design of the clinical candidate molecules for human studies.   I will also briefly mention our related work on engineered human enzymes for the treatment of inborn error of metabolism diseases.  

Relevant publications:
1)    Cramer, S.L., et al. “Systemic Depletion of L-Cyst(e)ine with Cyst(e)inase Increases Reactive Oxygen Species and Suppresses Tumor Growth,” Nature Medicine 23120-127 (2017)
2)    Triplett, T.A. et al. “Reversal of Indoleamie 2,3-Dioxygenase-Mediated Cancer Immune Suppression by Systemic Kynurenine Depletion with a Therapeutic Enzyme,” Nature Biotechnology 36:758-764 (2018)
3)    Wang, W., et al. “CD8+ T Cells Regulate Tumour Ferroptosis During Cancer Immunotherapy” Nature 569:270-274 (2019)
4)    Lu, W-C. et al., “Enzyme-Mediated Depletion of Serum L-Met Abrogates Prostate Cancer Growth via Multiple Mechanisms without Evidence of Systemic Toxicity, “Proc. Natl. Acad. Sci. USA 117:532-540 (2020) 

Bio:

George Georgiou is the Dula D. Cockrell Centennial Chair and Professor at UT Austin, Dep. of Chemical Engineering and Molecular Biosciences. He has authored >280 publications and is co-inventor of >150 issued and pending US patents, licensed to 29 pharma & biotech companies.  Dr. Georgiou is an elected member of the National Academy of Engineering (2005), National Academy of Medicine (2011), National Academy of Inventors (2015) and the American Academy of Arts and Sciences (2016).  In 2013 Georgiou was selected as one of the top 20 Translational Researchers by Nature Biotechnology.

Dr. Georgiou founded GGMJD in 1999 (acquired by Maxygen in 2000), Aeglea Biotherapeutics in 2013 (NSDQ: AGLE) and Ikena Oncology (NSDQ: IKNA) and served on the Board of Directors of both AGLE and IKNA.

Dr. Georgiou’s research is focused on: (i) the molecular level understanding of human adaptive immunity in infectious diseases and in autoimmunity; (ii) the discovery/preclinical development of protein therapeutics and (iii) the biology of Fc receptors and the engineering of therapeutic antibodies with improved effector functions.

Notably, he is co-inventor of 5 protein therapeutics that are approved or in clinical/late-stage preclinical evaluation: olbitoxaximab, pegzilarginase (phase III), AGLE-177 (phase I) IK-412 and cyst(e)inease.