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Developing new Diagnostics and Therapeutics for an Immune Checkpoint

Investigators: Richard Roberts; Mitchell Gross; Terry Takahashi

The use of antibodies as immune checkpoint inhibitors has shown outstanding results in the clinic. However, the antibodies are large molecules and are slow to diffuse into tumors, resulting in poor tumor uptake and penetration. We have developed small, protease resistant peptides called SUPR Peptides that bind with antibody-like affinities and specificities. Because they are >50-fold smaller than antibodies, SUPR peptides have pharmacokinetic properties that are similar to small molecules, and thus will have better tumor penetration. Here, we propose to develop SUPR peptides against Programmed Death Ligand 1 (PD-L1) that is often expressed on tumor cells to avoid immune destruction. We will engineer high affinity, highly specific PD-L1- binding SUPR peptides. These peptides will then be tested to validate that they can recognize PD-L1 on cells. Lastly, we will test if these peptides are capable of detecting PD-L1 in patient derived lung cancer tissue and compare the detection of PD-L1 to a commercially-available antibody.