Project 463373

Chimeric Antigen Receptor (CAR) T cell therapy is relatively new and exciting form of cancer therapy which uses a patients own re-programmed immune cells to specifically target and destroy cancer cells. In this treatment, T cells (a type of immune cell) are harvested from a patients blood and re-programmed in a laboratory to express a protein called a Chimeric Antigen Receptor, which enables them to recognize and destroy specific types of cancer cells. These CAR T cells are then re-infused into the patient where they attack and destroy the cancer cells, which can result in disease remission. Several treatments have been approved by the FDA to date. The current methods of generating CAR T cells in the lab involve genetic manipulation using viruses, and the engineered cells are not the same as natural T cells, which can cause significant problems in patient treatment; further, harvesting the T cells from blood is expensive and arduous for the patient. Here, we propose to deliver the instructions for T cells to make a CAR directly in the body by using lipid-nanoparticle(LNP)/CAR-mRNA complexes, similar to the current COVID-19 mRNA vaccines. By optimizing the composition of these LNP/mRNA complexes, it is possible to enable mRNA delivery to specific tissue and cell types. The objective of these studies is to develop a method for delivery of CAR mRNA directly to T cells via lipid-nanoparticle based delivery, potentially removing significant treatment barriers to patients.