Chimeric proteins and methods for using the same
Novel chimeric proteins are disclosed. The proteins comprise at least two portions. The first portion binds to a first cell and decreases the cell's ability to send a trans signal to a second cell; the second portion sends its own trans signal to the second cell. Methods for making and using these proteins in the treatment of cancer, viral infections, autoimmune and alloimmune diseases are also disclosed, as are pharmaceutical formulations comprising the novel chimeric proteins and genes. Either the proteins themselves or a genetic sequence encoding the protein can be administered. Other methods are also disclosed in which two molecular components result in decrement of a first trans signal from a first cell and the conferring of a second trans signal to a second cell.
1. A chimeric protein comprising:
a first protein that binds to at least one surface molecule on a first cell and results in the decrement of a first trans signal from said cell; and
a second protein that binds to at least one surface molecule on a second cell and sends a second trans signal to said second cell, wherein the first and second trans signals sent from the surface of said first and second cells are not the same, and wherein when the first protein is selected from the group consisting of CTLA-4, CD27, CD40, and ICOS and second protein is selected from the group consisting of FasL, TRAIL, TWEAK, CAR, CD8, PP14, BAFF/TALL-1/THANK/BLys, PD-1 and RCAS1.
2. The chimeric protein of claim 1 , wherein said first protein is CTLA-4 and said second protein is FasL.
3. A pharmaceutical formulation comprising the chimeric protein of claim 1 or 2 in a suitable pharmaceutical carrier, wherein said pharmaceutical formulation is administered in unit dosage form to a patient in need thereof in therapeutically effective amounts.