Events

Cancer cells have dysregulated metabolism, resulting in the accumulation of metabolic byproducts in tumors. These accumulated metabolites can directly inhibit the antitumor function of immune cells. More specifically, the ribonucleoside adenosine accumulates in tumors to levels 1000-fold higher than compared to healthy tissues and negatively impacts nearly every aspect of antitumor T cell immunity. Here, we will detail our lab’s ongoing efforts to prevent the impact of adenosine using two synthetic control strategies to rewire tumor metabolism.  First, we will describe our efforts to engineer T cells that actively remodel their extracellular metabolic environment through the secretion of an ‘enzyme weapon’ that degrades adenosine. We will also discuss development of engineered synthetic promoters that are activated by tumoral adenosine, allowing for creation of cancer-activated genetic switches. Secondly, we will show how administration of an engineered adenosine degrading enzyme directly to cancers can prevent adenosine-immunosuppression, slowing tumor growth. Through these examples, we will demonstrate the potential of two uncommon methodologies to impact antitumor immunity, both geared towards applying concepts of metabolic engineering and control to cancers. In addition, we will discuss ongoing efforts to develop new cellular engineering and transcriptional control tools.

Dr. Johnny Blazeck is an Assistant Professor of Chemical and Biomolecular Engineering at Georgia Tech. He completed his Ph.D. in Chemical Engineering at the University of Texas at Austin under the direction of Dr. Hal Alper, and then stayed at UT Austin, but joined the lab of Dr. George Georgiou to perform his postdoctoral training in immunoengineering. Dr. Blazeck was awarded a NIH New Innovator Award and a Georgia Tech CTL/BP Junior Faculty Teaching Excellence Award in 2022, as well as a Beckman Young Investigator Award in 2020.  His lab has two broad, ongoing efforts: (1) developing therapeutic proteins and cells that improve the antitumor response by remediating dysregulated metabolism and (2) performing high throughput synthetic biology studies in yeast and human cells.