Clinical Translation of Off the Shelf CLL1 Targeted CAR-Vd2 T Cells for AML
Acute myeloid leukemia (AML) is a serious blood cancer that mainly affects children and young adults. Even with intensive chemotherapy and stem cell transplantation, many patients relapse or experience severe long term side effects. New immune based treatments, such as CAR T cell therapy, have been highly successful for some leukemias, but results in AML have been limited. This is largely because AML cells vary widely in the proteins they express, allowing some cancer cells to escape treatment. In addition, most CAR T therapies rely on cells collected from the patient, which can take weeks to manufacture and may be poorly functional in very sick individuals.
This project focuses on a different type of immune cell called Vd2 gamma delta (?d) T cells, which are naturally equipped to recognize and kill cancer cells through multiple mechanisms. Importantly, these cells do not cause immune incompatibility, making them suitable for “off the shelf” use from healthy donors. By genetically enhancing these cells with a leukemia targeting CAR and a novel persistence boosting receptor, the proposed approach is designed to overcome cancer cell diversity, improve treatment durability, and provide faster access to therapy for patients with AML.
Project Goals
The goal of this project is to develop a ready to use, donor derived immune cell therapy for children and young adults with acute myeloid leukemia. The research aims to produce large numbers of highly effective Vd2 ?d T cells that are genetically engineered to recognize leukemia cells while also surviving and functioning longer in the body. Unlike traditional CAR T therapies made individually for each patient, this approach will create banked cell products from healthy donors that can be given quickly when treatment is needed.
Specifically, the project will (1) establish a manufacturing process that meets strict clinical standards and allows large scale production of these cells, and (2) identify the healthiest donors whose cells show the strongest anti leukemia activity. By combining multiple cancer killing mechanisms in a single cell product, this strategy is designed to eliminate diverse leukemia cells and reduce the risk of relapse. Successful completion of this work will lay the foundation for clinical trials and could lead to safer, faster, and more effective immune therapies for patients with AML.
