2019 Winner: Dissecting the impact of signaling strength on T cell function using chimeric antigen receptors

Project Information
Dissecting the impact of signaling strength on T cell function using chimeric antigen receptors
Engineering
BME 195
The purpose of this research is to study the impact of signaling strength on human T cell function. A chimeric antigen receptor (CAR) is an artificial immune receptor that allows T cells to recognize specific antigens on a targeted tumor cell. A CAR contains an extracellular antigen binding domain and an intracellular signaling domain. The T cell receptor (TCR) is a complex of proteins that aids in the activation of T cells in response to their cognate antigen. A CAR signaling domain typically comprises the costimulatory molecule CD28 and the zeta chain of the TCR, which contains 3 signaling motifs knowns as ITAMs: immunoreceptor tyrosine-based activation motifs. To dissect the contribution of signaling strength to CAR T cell function, a series of second generation 28-zeta CARs featuring TCR zeta chains with different ITAM mutants was created. Wild-type and mutant 28-zeta CAR-mediated signaling was then compared in primary human effector T cells. I found that CD3-zeta ITAMs are required for CAR-mediated T cell activation. Ongoing work aims to more comprehensively assess the role of ITAM identity and quantity on CAR T cell function.
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Students
  • Lilian Eden Yao (Ten)
Mentors