UC San Francisco

“Engineering best-in-class chimeric antigen receptor T-cell (CAR-T) therapies for AML by
targeting CD70 and active integrin beta-2”

ABSTRACT

Acute Myeloid Leukemia (AML) is a devastating disease with <30% 5-year survival on current treatment regimens. This cancer, diagnosed in >20,000 Americans per year, has an urgent need for new therapeutic strategies. One of the most exciting new treatment strategies for blood cancers are Chimeric Antigen Receptor (CAR) T cells, which have led to cures in patients with B-cell origin malignancies who previously had dismal prognoses. CAR-T functionality and efficacy in AML appear to be limited by several hurdles: 1) lack of a highly disease specific antigen due to immense heterogeneity of the AML tumor microenvironment (TME) 2) elevated
on target-off tumor toxicities where potential therapeutic targets are also expressed on healthy hematopoietic blood cells 3) and the presence of AML TME factors that impede T-cell persistence and lead to antigen positive relapse. My long term goal in this proposal is to develop a cellular therapy platform to overcome these hurdles plaguing AML CAR-T products by incorporating highly safe and effective target antigens and T-cell activating modifications in the engineering design.