Immunoengineering Seminar Series

Bringing together members of the bio community interested in and doing research in immunoengineering.

"Leveraging Enzymatic Elimination of Immunosuppressive Adenosine to Extend Survival in a Murine Colorectal Cancer Model"

Maria Jennings
Graduate Student - John Blazeck, Ph.D., Advisor
Georgia Tech

ABSTRACT
Adenosine is a small molecule that counteracts inflammation. Under normal conditions, adenosine calms immune cells to allow healing following trauma or infection. Yet unlike normal cells, cancer cells generate abnormally high levels of adenosine that keep immune cells from destroying them. Additionally, the inflamed tumor landscape supports increased expression of adenosine receptors on both cancer and immune cells. In tumors, high adenosine concentrations coupled with increased adenosine receptor density result in the following: 1) suppressed immune cells are unable to attack tumors, and 2) adenosine signaling encourages cancer cells to make more adenosine. I report the development of a human enzyme, Homo sapiens adenosine deaminase I (HsADA1), to reduce adenosine concentrations in tumors. HsADA1 degrades adenosine so efficiently that the process is limited by how quickly adenosine can diffuse into the enzyme rather than the enzyme’s ability to act upon it. When administered to mice with tumors, HsADA1 slows tumor growth and extends the lifespan of treated mice relative to mice provided placebo. Following resolution of HsADA1’s structure, we mutated the enzyme for enhanced stability at conditions like those in the body. I will further discuss ongoing efforts to better HsADA1 functionality as a cancer therapeutic and the subsequent impact on tumor mouse models. From a 30,000-foot view, I intend to demonstrate the efficacy of adenosine depletion as a therapeutic strategy for the treatment of solid cancers through my work with HsADA1.
 

Upcoming Immunoengineering Trainee Seminars - Spring 2022
March 4 - Maggie Brown & Erin Connolly (Gibson Lab) and Grazia Marsico (Singh Lab)
April 15 - Maggie Manspeaker (Thomas Lab) and Fredrick Bulondo (Babensee Lab)

The goal of this series is to enhance our Immunoengineering community here at Georgia Tech and to include involvement from Emory participants at regular intervals. Seminars will feature one or two research presentations by graduate students and postdoctoral fellows, followed by lively discussion.

If you have any questions or are interested in being a speaker, please contact Karen Martin, Abir Muhuri, or Belinda Joseph. Thanks!