Institute for Bioscience and Biotechnology Research bags NIH grant to investigate T cell biology for biotherapeutics development

A team of investigators from theInstitute for Bioscience and Biotechnology Research (IBBR)and theUniversity of Pittsburghrecently received a$3.6MNational Institutes of Health award to expand the scope of their T cell research.


IBBR FellowDr.Roy Mariuzza(Professor, UMCP Department of Cell Biology & Molecular Genetics) and collaborator Dr.Dario Vignali, Professor and Vice Chair of the Immunology Department at theUniversity of Pittsburgh, will work to further characterize LAG3 -- a well-known inhibitory receptor on T cells. LAG3 activity has been implicated in various cancers, as well as in the chronic infections associated with malaria and HIV.


The human immune system fights infectious agents and protects us from cancer. But, this powerful system requires many mechanisms of self-regulation to minimize damage to our own tissues through autoimmune diseases and excessive inflammation. An important part of the checks and balances of the immune system involves "immune checkpoint molecules," receptors on immune cells that turn down the immune response.


Pathogens and tumor cells thrive, in part, by engaging these immune checkpoint molecules, making them important drug targets in the fight against infectious disease and cancer. However, "the immune system is famously complicated and intricate," says Dr. Mariuzza, "so blocking a single checkpoint is unlikely to be effective for all applications." LAG3 is emerging as an important member of the immune checkpoint family of proteins with potential as drug targets.


Dr. Mariuzzahas expertise in the structural biology of immune system proteins, including T cell receptors (TCR), antibodies, and MHC proteins. His group will determine the 3D structure of LAG3 bound to various molecules. This will provide structural insight into the function of LAG3, to support the development of new biotherapeutics that might inhibit, or activate, this important immune checkpoint molecule. Pharmaceutical companies with anti-LAG3 therapies in their development pipelines include Bristol-Myers Squibb, Boehringer Ingelheim, Regeneron, and Novartis.


The LAG3 project complements IBBR's growing T cell program which, in addition to integrating multiple state-of-the-art structural biology methods, also includes development and application of computational modeling tools for predicting how T cell receptors recognize and bind to their targets.

IBBR and the University of Pittsburgh recently received a $3.6M National Institutes of Health award to expand the scope of their T cell research

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