Abstract 3776: Generation and formatting of an Affimer® biotherapeutic for the inhibition of the PD-L1/PD-1 pathway: Proof of concept in mouse

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.3776-3776
• Main Authors: Basran, Amrik, Stanley, Emma
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-3776

We have generated a range of potent Affimer antagonists to both human and mouse programmed death-ligand 1 (PD-L1) and have demonstrated that when formatted, possess the necessary affinity, pharmacokinetics (PK) and tissue penetration to modulate the immune system and demonstrate efficacy in mouse models. Affimer biotherapeutics are a new protein scaffold with great potential for the generation of biotherapeutics. Based on the human protease inhibitor Stefin A, the scaffold is small (12kDa), lacks any post translational modifications such as disulphide bonds and glycosylation. Large diverse phage display libraries have been created by engineering in two 9 amino acid peptide loops into the scaffold backbone. Using phage display, we have identified competitive binders to both mouse and human PD-L1 which are low single digit nM in affinity as determined by Biacore. By ELISA we have shown that the Affimer molecules identified compete against PD-1 and CD80 for the binding site on PD-L1 and bind to the target on a range of human cancer cell lines (e.g. lung adenocarcinoma cells), as demonstrated by FACs. Following formatting of the lead Affimer protein to the N-terminal Fc region of an IgG, we showed that we could further improve the affinity to give a KD of