Engineering T cells in vivo to express a synthetic cytokine receptor enables preferential expansion and enrichment of anti-CD22 CAR T cells.
TL;DR
Preclinical studies are described demonstrating that UB-VV400 generates anti-CD22 CAR T cells that kill CD22-expressing B cells and tumor cells in vitro and in vivo, and that engagement of RACR results in the selective expansion and enrichment of CAR T cells in vivo leading to complete tumor clearance and B cell depletion.
Abstract
Ex vivo-manufactured chimeric antigen receptor (CAR) T cells targeting CD19 have transformed treatment strategies for patients with B cell malignancies and shown promising results in autoimmune disease. Yet despite their success, significant barriers remain that impede patient access to these therapies, including their complex manufacturing and the need for lymphodepleting chemotherapy. Moreover, many patients who receive ex vivo-manufactured CD19 CAR T cells do not achieve durable responses, suggesting that the expansion and persistence of CAR T cells may need improvement, and/or that strategies targeting alternative antigens may be needed for patients who are refractory to or relapse following treatment with CD19-directed therapies. Umoja is developing a surface-engineered lentiviral vector (LVV) platform capable of generating CAR T cells in vivo without lymphodepletion. UB-VV400 delivers a payload comprised of a fully human anti-CD22 CAR and the rapamycin-activated cytokine receptor (RACR), which enable preferential expansion and enrichment of CAR T cells in response to rapamycin. Here, we describe preclinical studies demonstrating that UB-VV400 generates anti-CD22 CAR T cells that kill CD22-expressing B cells and tumor cells in vitro and in vivo, and that engagement of RACR results in the selective expansion and enrichment of CAR T cells in vivo leading to complete tumor clearance and B cell depletion.