Daniel Lee, MD

Funded by the V Foundation’s Virginia Vine event

Chimeric antigen receptor (CAR) T-cells are immune cells from patients that are engineered to target and kill cancers (not normal tissue).  This is a new and exciting way to treat cancer. CARs have been wildly successful in treating children with leukemia that does not respond to any other therapy, saving many lives.  I ran one of the first clinical trials to show this.  Sadly, many patients experience severe or life-threatening side effects.  The only drug that helps is currently on national shortage.  This means some patients needing this lifesaving therapy may not get it.  Even if that drug was available, CAR therapy still needs to be safer.  We developed a chimeric inhibitory receptor (CIR) that we believe does just that.  When it is combined with a CAR it dramatically decreases the production of the side effect causing proteins called cytokines.  Importantly, it still kills tumors.  Funding from this grant will allow us to make more versions of the CIR that can put the brakes on CARs in different ways.  We will test the best ones in mice that have leukemia to confirm they still work.  Results from these experiments will allow us to start a clinical trial of CIR-containing CAR T-cells for patients with leukemia or lymphoma here at the University of Virginia using our new CAR T-cell manufacturing facility.  This unique approach to improving safety will have a dramatic impact on Virginians as well as all others with cancer who need life-saving CAR T-cell therapy. 

Location: UVA Health System Cancer Center - NC
Proposal: Development of a self-regulating feedback system of Chimeric Antigen Receptor T cell activity in response to specific circulating toxicity-associated inflammatory mediators
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