CARs provide a synthetic approach to controlling T cell antigen specificity by combining the antigen binding domain of a monoclonal antibody (in the form of a scFv) with the signal transduction domains of an antigen receptor (TCR-zeta) in a single molecule.  Originally conceived by Zelig Eshhar at the Weizman Institute, a number of different CAR designs that also incorporate co-stimulatory signal transduction domains such as from CD28, 4-1BB, OX-40, ICOS and others have been described.  These receptors can be artificially expressed in human T cells using gene transfer techniques including lentiviral transduction. The CD19-specific CAR used in adoptive immunotherapy of patients with chronic lymphocytic leukemia and acute lymphoblastic leukemia [1-2] is an example of a CAR developed by the laboratory[3]

1. •[1]Porter et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med (2011) vol. 365 (8) pp. 725-33
   

2. •[2]Kalos et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med (2011) vol. 3 (95) pp. 95ra73
   

3. •[3] Milone et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther (2009) vol. 17 (8) pp. 1453-64
   

Ongoing projects in the laboratory include:

1. •development of CARs with new target specificities for application in other cancers
   

2. •development of regulated CARs to enhance cancer specificity over normal tissues
   

3. •development of new CAR platforms with enhanced function