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This project will address the many limitations of autologous CAR-T therapies, such as accessibility, affordability, wait period and manufacturing failures by developing an allogeneic CAR T approach that would be applicable to T/NK cell malignancies and other cancers while also resisting immune rejection by the recipient¡¯s immune system.

To address the challenge of lack of defined and targetable surface tumor antigens beyond B cell malignancies, we will target intracellular tumor antigens using a novel multimeric NanoCAR against acute myeloid leukemia (AML). By targeting several antigens simultaneously, we aim to reduce the chance of tumor escape and improve durability of response. 

We will tackle the barrier to migration and infiltration of CAR T cells into tumors by

1. endowing them with synthetic receptors that enable preferential extravasation at tumor sites
2. enabling expression of enzymes to degrade and remodel the extracellular matrix in pediatric neuroblastoma and medulloblastoma
   

This project will tackle metabolic dysfunction of CAR T cells in the tumor microenvironment by engineering them to enhance their expansion, trafficking and function in the tumor microenvironment and improve antitumor efficacy in colorectal cancer.