Cancers of the blood account for an estimated 8% of all cancers in adults, with 5-year survival projections as low as 47%. Treatment costs can surpass $800,000 in acute cases, with an average of $200,000 spent during the first two years of treatment. As the population ages, doctors anticipate a rise in the number of hematological malignancies and an increased demand for safe, effective means of treating these difficult-to-treat cancers. Chimeric antigen receptor (CAR) T cells are an emerging technology that have revolutionized cancer treatment, but an estimated 50% of patients do not respond to CAR T cell therapy. In nearly half of these cases failure is due to decreased persistence of the re-infused cells.
Description
Cultured T cells capable of performing oxidative metabolism are more fit for the metabolic conditions they will encounter in vivo, such that promoting oxidative metabolism will increase their in vivo persistence. Oxidative metabolism also inversely correlates with how differentiated a cell becomes, which further impacts their survival. Thus, a major goal of cellular therapies has been to make effector cells both less differentiated and more oxidative before transfer into recipients. Increasing signaling through the cellular energy sensor AMP-activated protein kinase (AMPK) upregulates oxidative metabolism in human T cells while keeping them less differentiated. These changes are expected to increase both the durability and function of cellular therapies by promoting T cell longevity. By overexpressing the regulatory component of the AMPK heterotrimeric complex via lentiviral transduction, Pitt researchers propose to modulate AMPK activity and thereby improve the efficacy of multiple therapeutic interventions dependent upon T cells.
Applications
· Increasing the efficacy of T cell therapy for treating cancer
· Preventing or treating autoimmune diseases
· Treating graft-versus-host disease
· Preventing rejection following solid organ transplantation
Advantages
· Improved in vivo persistence of ex vivo and in vitro manipulated effector T cells
· Increased in vitro expansion of T cells during the culture period
· Increased stability and suppressive functionality of regulatory T cells
· May make adoptive cellular therapies effective for an estimated 20% of unresponsive patients
Invention Readiness
In vitro data
IP Status
https://patents.google.com/patent/US20230392117A1
