Chandrabali Bhattacharya, PhD, MSc
Development of T Cell Targeting Lipid Nanoparticle System for In Vivo CAR T Cell Therapy Applications
Abstract
CAR T-cell therapy or ‘living drug’ has shown unprecedented clinical response against refractory and relapsed acute lymphoblastic leukemia cases with complete remission. This is expensive ($500k) and involves modification of the patient’s T cells outside the body and reinjection. Moreover, T cells are notoriously difficult to modify and require electroporation or virus-mediated processes, which can result in membrane disruption, loss of cytoplasmic content, and lower yield. Surviving cells may experience cytotoxicity and altered protein expression, leading to side effects in treatment. Lipid nanoparticles are a promising alternative, but cargo size and functionality need optimization for T-cell endocytosis. In this proposal, we seek to tune lipid nanoparticles with carbohydrates to develop an in vivo CAR T cell therapy platform that could bypass the requirement of adoptive cell transfer and activate T cells in the body with a single injection.
I am absolutely thrilled to have been awarded the Faculty Starter Grant in Drug Delivery. This grant will be instrumental in enabling my lab to develop a lipid nanoparticle platform that can selectively carry CAR mRNA to T cells. This technology could potentially lead to an in vivo CAR system that would eliminate the need for adoptive cell transfer with just a single injection. I am extremely grateful for this opportunity and excited to see where this research will take us.
