Every day, millions of T cells navigate through the human body, on the lookout for any signs of invaders. Each T cell is equipped with a unique T cell receptor, meticulously designed to identify foreign antigens.
To simplify the complex process of how these T cells detect their targets, MIT Associate Professor Michael Birnbaum has pioneered advanced tools that enable the simultaneous study of vast numbers of these interactions.
Understanding these intricate interactions holds the promise of discovering innovative ways to reprogram T cells to specifically target antigens, including the mutations present in a cancer patient’s tumor.
“T cells are incredibly diverse in their recognition capabilities and functions. While significant progress has been made in understanding these mechanisms on a case-by-case basis, our goal is to comprehend the entire process at a level of sophistication akin to our understanding of individual components. With this knowledge, we can enhance our ability to manipulate these interactions to combat disease,” Birnbaum explains.
This innovative approach could revolutionize immunotherapy techniques for cancer treatment, alongside developing potential new therapies for autoimmune diseases like type 1 diabetes and viral infections such as HIV and COVID-19.
Passion for Immunology
Birnbaum’s fascination with immunology ignited during his high school years in Philadelphia, where a program allowed students to engage in lab research. Beginning in tenth grade, he immersed himself in immunology research at the Fox Chase Cancer Center.
“It gave me exposure to many concepts I study today, confirming my desire to pursue this field,” Birnbaum recalls.
During his undergraduate studies at Harvard University, he enrolled in a newly created major, chemical and physical biology. An introductory immunology course captivated him, leading him to earn a PhD in immunology at Stanford University, where he began exploring how T cells recognize target antigens.
T cell receptors are protein complexes located on the surfaces of T cells, composed of gene segments that can be recombined to create up to 1015 unique sequences. When a T cell receptor identifies a foreign antigen, it triggers the T cell to multiply and initiate the process of eliminating cells presenting that antigen.
As a graduate student, Birnbaum focused on creating tools for large-scale studies of T cell and antigen interactions. After obtaining his PhD, he took a one-year postdoctoral position in a neuroscience lab at Stanford but soon realized his passion lay with immunology.
In 2016, he became a faculty member in MIT’s Department of Biological Engineering and the Koch Institute for Integrative Cancer Research, attracted by the collaborative spirit at MIT, which encourages tackling challenging and impactful problems.
“At MIT, there’s a unique boldness in addressing these issues, especially within the immunology community, which is both exceptionally talented and incredibly supportive,” he notes.
Innovative Detection Techniques
At MIT, Birnbaum’s research lab is dedicated to exploring T cell-antigen interactions, with aspirations to reprogram these interactions to combat diseases like cancer. In 2022, he unveiled a groundbreaking technique for analyzing these interactions on a grand scale.
Traditionally, available tools allowed researchers to study either a large pool of antigens exposed to a single T cell (or B cell) or groups of immune cells interacting with a limited number of antigens. Birnbaum’s new method utilizes engineered viruses to present a vast array of antigens to extensive populations of immune cells, facilitating the simultaneous screening of comprehensive libraries of both antigens and immune cells.
This innovative strategy could permit researchers to screen thousands of antigens against an entire individual’s population of B and T cells, potentially uncovering why certain individuals can naturally fend off specific viruses like HIV more effectively than others.
Birnbaum also aims to discover methods to reprogram T cells within a patient’s own body. Currently, T cell reprogramming necessitates extracting T cells from a patient, genetically modifying them, and reinfusing them. However, this could be streamlined by directly reprogramming T cells using the same viruses used in Birnbaum’s screening technology. He co-founded a company named Kelonia, which is dedicated to advancing this vision.
To further model T cell interactions on a larger scale, Birnbaum is collaborating with a global team using artificial intelligence to predict T cell-antigen interactions. This research group, which he leads, comprises 12 laboratories from five countries, funded by Cancer Grand Challenges. They aspire to develop predictive models that could help design engineered T cells for various treatments.
“The aim is to explore whether such predictions can be made, and if successful, it could drastically improve our understanding of which immunotherapies are most effective for different individuals. This knowledge may advance personalized vaccine and T cell therapy designs,” Birnbaum states.
Photo credit & article inspired by: Massachusetts Institute of Technology
