Soluble CD80 as a therapeutic to reverse immune supression in cancer patients
The present invention provides for a therapeutic cancer treatment using a soluble CD80 fusion protein that binds to PDLL and inhibits PDLL-PD1 interactions thereby overcoming PDLL-induced immune suppression and restoring T cell activation.
1. A method to inhibit or reduce binding of PD-L1 to PD-1, the method comprising:
providing a composition consisting essentially of a soluble chimeric polypeptide in a pharmaceutical carrier wherein the composition is formulated for parenteral administration to a subject, wherein the soluble chimeric polypeptide comprises a CD80 sequence fused to a Fc of a IgG1 sequence in the pharmaceutical carrier, wherein the CD80 sequence consists of the amino acids of SEQ ID NO:4; and
contacting a tumor cell of the subject with the composition and soluble chimeric polypeptide; and
detecting binding of the soluble chimeric polypeptide to PD-L1 positioned on the tumor cell, wherein the soluble chimeric polypeptide inhibits or reduces the binding of PD-L1 to PD-1.
2. The method of claim 1 , wherein the soluble chimeric polypeptide further comprises a linker positioned between the CD80 sequence and Fc of IgG1.
3. The method of claim 1 , wherein the CD80 sequence is fused directly to the sequence of Fc of IgG1.
4. The method of claim 1 , wherein the tumor cell is within a human subject.