Chimeric Receptors Providing Both Primary and Costimulatory Signaling in T Cells from a Single Gene Product

摘要: Single chain Fv chimeric receptors, or T-bodies, are described with intracellular sequences comprising the costimulatory signaling domain of CD28 in series zeta-chain from TCR complex. Using an engineered human single derived P67, mAb specificity for CD33, and a spacer Ab hinge region either Fcgamma part extracellular region, fusion molecules were constructed to test ability designs mediate both primary costimulation one binding event. Constructs proximal distal membrane found express more efficiently Jurkat than constructs opposite orientation capable mediating up 20 times IL-2 production on stimulation solid phase Ag when compared transfectants expressing receptors domains only. was specific challenge completely inhibited by incubation free same as site construct, but not isotype-matched control Ab. The these proteins shown be p85 subunit phosphatidylinositol 3'-kinase. These represent first new generation gene multidomain specifically recognition