A CD2 CD28 CHIMERIC RECEPTOR TRIGGERS THE CD28 SIGNALING PATHWAY IN CTLL.2 CELLS/

We are evaluating strategies to enhance the in vivo proliferation and function of adoptively transferred antigen-specific T cells. Although the CD28 costimulatory pathway is important for T cell activation and proliferation, the expression of the ligands for CD28 is highly restri cted. We have generated a chimeric receptor composed of signaling doma ins of CD28 and the extracellular domain of CD2 which binds the widely expressed ligand CD58. The CD2/CD28 chimeric receptor was introduced into CTLL.2 cells via retrovirus infection and was shown to be express ed on the cell surface. By monitoring early and late components of the CD28 signaling pathway the chimeric receptor was demonstrated to trig ger the CD28 pathway in response to CD2 cross-linking. The possible ut ility of the CD2/CD28 chimeric receptor for adoptive immunotherapy is discussed.