CD86 variants with improved affinity for CTLA-4
The invention provides a polypeptide that specifically binds to CTLA-4, particularly human CTLA-4.
1. A polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID Nos: 6 to 24, wherein said polypeptide binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) with higher affinity than wild-type human cluster of differentiation 86 (CD86).
2. The polypeptide according to claim 1 , wherein the ratio of either
(a) [K d for cluster of differentiation 28 (CD28)]÷[K d for CTLA-4]; or
(b) [EC 50 for CD28]÷[EC 50 for CTLA-4]is higher than the corresponding ratio of wild-type human CD86.
3. The polypeptide according to claim 1 , wherein said polypeptide inhibits signalling from CTLA-4 or increases the activity of a cell expressing CTL-4, and optionally wherein said CTLA-4 is human or murine CTLA-4.
4. The polypeptide according to claim 1 , wherein said polypeptide is attached to a molecule selected from the group consisting of an immunoglobulin fragment crystallisable (Fc) region, an immunoglobulin (Ig) domain, polyethylene glycol (PEG), a therapeutic agent and a detectable label.
5. A composition comprising a polypeptide according to claim 1 and at least one pharmaceutically acceptable diluent or carrier.
6. A method of increasing the activation of a cell expressing CTLA-4, the method comprising administering to said cell a polypeptide according to claim 1 .