Weishan Huang
LSU, School of Veterinary Medicine, Department of Pathobiological Science
Project Title
Modulation of TCR signaling for sustainable CAR-T therapy
Funding Period
Pilot (June 7, 2022 - February 28, 2023)
Biosketch
Dr. Huang received a PhD degree in pharmacology and postdoctoral training in immunology at Cornell University. She was appointed assistant professor of immunology at LSU in 2018. Her research focuses on understanding the development and function of regulatory immunity and immune memory, with an overarching interest of developing T cell-based therapies against inflammation and cancer.
Abstract
Immunotherapy has shown the promise to cure cancer by infusing patients with tumor-specific anti-cancer immune cells, with demonstrated success of chimeric antigen receptor (CAR)-T cell therapy. CAR-T therapy has been successful in B cell (CD19+) malignancy, including acute and chronic lymphoblastic leukemia (ALL and CLL) and non-hodgkin's lymphoma. However, the cytotoxic and short-lived nature of CAR-T cells results in severe side effects of immunopathology and reduced the therapeutic values of this costly therapy. There is an urgent need of novel strategies for targeted immune modulation to elicit potent and persistent tumor-specific effector and memory T cell responses and minimize off-target toxicity. T cell development, function and homeostasis are regulated by T cell receptor (TCR) signals and cytokines and suggested to be proportional to TCR signal strength. However, very strong TCR activation and cytokine stimulation could lead to excessive cytotoxic T cell activation that can cause immunopathology while the anti-tumor immunity quickly exhausts. In this pilot program, Huang proposes to tune TCR downstream signaling in human CAR-T cells and to use pre-clinical mouse models to further develop strategies that can enable a more sustainable and less toxic CAR-T therapy.