Monoclonal antibodies e.g. Ipilimumab, Atezolizumab, have successfully shown that blocking cellular interactions that negatively regulate T-cell immune responses can amplify pre-existing immunity to cancer.  

Avacta have screened and identified Affimer molecules that recognize human programmed death-ligand 1 (PD-L1/AVA04 programme) to investigate the anti-tumour potential of the technology.  We identified clone AVA04-182 as a surrogate for in vivo mouse studies given  that none of the human PD-L1 binding Affimers recognized mouse PD-L1.  The molecule was fused to the Fc portion of a human IgG1 (AVA04-182hFc1) to extend half life and the binding properties evaluated by Biacore® and flow cytometry.  Competitive ELISA confirmed disruption of the interaction between PD-L1 and PD-1.  AVA04-182hFc1 was well tolerated in mice at all tested doses and showed statistically significant reduction of tumour growth in the CT-26 syngeneic model.  Competitive ELISA has shown AVA04-182hFc1 to recognize the same epitope region as a commercially approved immunotherapy confirming the potential of the Affimer technology for immuno-oncology therapeutics.