Surface-bound antigen binding portions of antibodies that bind to ctla-4 and cd28 and uses therefor

摘要

The instant invention provides compositions for downmodulation or upmodulation of the immune response. For example, constructs comprising an exposed surface having attached to it i) an antigen-binding portion of an antibody that binds to a CTLA-4 or CD28 molecule that is expressed on a T cell of the subject, and ii) an MHC molecule selected from the group consisting of: a class II molecule that is syngeneic to the subject, a class I molecule that is syngeneic to the subject, and a class I molecule that is allogeneic to the subject are provided. Methods of using the molecules of the invention in downmodulation or upmodulation of the immune response are also provided. Also provided are methods of downmodulating a immune response in a subject comprising causing a cell of the subject to express an antigen-binding portion of an antibody that binds a CTLA-4 or CD28 molecule that is expressed on a T cell of the subject, such that the immune response in the subject is dowmnodulated. Methods of preparing an allogeinc cell for transplantation and methods of transplanting engineered allogeinc cells are also provided.