Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence.

ABSTRACT:

Purpose

Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority of post-CD22 CART remissions are short and associated with reduction in CD22 expression. We evaluate the implications of low antigen density on the activity of CD22 CART and propose mechanisms to overcome antigen escape.

Experimental design

Using ALL cell lines with variable CD22 expression, we evaluate the cytokine profile, cytotoxicity, and in vivo CART functionality in the setting of low CD22 expression. We develop a high-affinity CD22 chimeric antigen receptor (CAR) as an approach to improve CAR sensitivity. We also assess Bryostatin1, a therapeutically relevant agent, to upre

SUBMITTER: Ramakrishna S 

PROVIDER: S-EPMC8290499 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature