In the past year, this project has consisted of testing multiple factors that could affect the function of chimeric antigen receptors (CARs). Chimeric antigen receptors consist of several components, the antigen-recognition moiety that is usually derived from a monoclonal antibody, a extracellular region that connects the antigen-recognition moiety to the transmembrane portion, costimulatory domains such as 4-1BB and CD28, and T cell activation domains such as CD3-zeta. We have constructed 10 new CARs over the past 6 months to test various components of CARs. T cells are transduced with the various CARs by using a gammaretroviral vector, and in vitro assays are carried out.
The aim i s to find CARs that impart T cells with the ability to kill cancer cells and proliferate without producing large amounts of potentially toxic inflamatory cytokines. We have found that changing the hinge region, costimulatory domains, or T cell activation domains all cause profound differences in CAR function. Following extensive in vitro testing, we will test promising CARs in a murine model within the next few months. This work is all at early stages, but hopefully it will lead to improved CARs for clinical testing within the next 1-2 years. Another aspect of this project is identification of new targets for CARs. We are assessing multiple targets that are expressed by leukemia and lymphoma as a main part of this project.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011417-04
Application #
8938106
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Magalhaes, Isabelle; Kalland, Ingrid; Kochenderfer, James N et al. (2018) CD19 Chimeric Antigen Receptor T Cells From Patients With Chronic Lymphocytic Leukemia Display an Elevated IFN-? Production Profile. J Immunother 41:73-83
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