Many microbial species colonize animals, with some species benefiting from their hosts without causing any harm. Some of these ‘commensal’ members of the microbiome can elicit a potent T cell response from their host’s immune system upon colonization.
In this talk, Michael Fischbach will describe two recent projects by his research group that aim to characterize and manipulate anti-commensal immune responses.
In the first project, he and his colleagues explored the functional properties of colonist-induced T cells by engineering the skin bacterium Staphylococcus epidermidis to express tumor antigens anchored to secreted or cell-surface proteins. Upon colonization, the engineered S. epidermidis elicited tumor-specific T cells that circulated, infiltrated local and metastatic lesions, and exerted cytotoxic activity. Their findings show that the immune response to a colonist can be redirected against a target of therapeutic interest by expressing a target-derived antigen in a commensal.
In the second project, they colonized germ-free mice with a complex defined community (made up of more than 100 bacterial strains) and profiled T cell responses to each strain individually. They found that T cell recognition of Firmicutes bacteria was focused on a widely conserved cell-surface antigen, opening the door to new therapeutic strategies in which colonist-specific immune responses are rationally altered or redirected.
Speaker Bio:
Fischbach is an associate professor in Stanford University’s Bioengineering Department and the Microbiology & Immunology Department. Additionally, he is an institute scholar at Stanford ChEM-H and director of the Stanford Microbiome Therapies Initiative. Fischbach is also a co-founder and director of Federation Bio and Viralogic, a co-founder of Revolution Medicines, a member of the scientific advisory board of NGM Biopharmaceuticals, and an innovation partner at The Column Group.
