Team Leader
Rong Fan, PhD – Yale University
Team Members
Stephanie Halene, MD, PhD Yale School of Medicine and Yale University |
Carl H. June, MD University of Pennsylvania Perelman School of Medicine |
Pablo G. Cámara, PhD University of Pennsylvania Perelman School of Medicine |
J. Joseph (“Jos”) Melenhorst University of Pennsylvania Perelman School of Medicine |
Project Summary
Immunotoxicity and autoimmune-like response is a significant problem hindering widespread use of cancer immunotherapies. Major players in the immune response are cytokines, which are substances secreted by some immune cells to affect other cells in response to a signal, e.g., recognition of a foreign body. To understand this response, the full spectrum of cytokine functions in a pre-infusion setting will be assessed and matched with patient responses to treatment with the chimeric antigen receptor (CAR) T therapy. Afterward, the function of the infused CAR T cells will be assessed to determine the mechanisms of efficacy and/or immune toxicity. The team also proposes identifying molecular characteristics underlying therapeutic efficacy and toxicity of CAR T therapy, and biomarker discovery by using computational models and machine learning that look at the data. If successful, this will create a “tool” that clinicians can use to mitigate patient risk associated with CAR T therapies while improving the chances of therapeutic success.