Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Our understanding of the immune system and its role in cancer biology have undergone profound changes within recent decades. There is now a wealth of opportunities to develop next-generation diagnostics and therapies for increased survival outcomes. Peptides are excellent therapeutic modalities. They are exceptionally well-suited for the design of highly specific targeted therapies. I will describe two novel approaches we have developed for design of potent lead peptides. (i) The first approach involved use of recombinant libraries to engineer bioactive cyclisation linkers to achieve a two-in-one effect of stabilisation and increased activity.¹ (ii) The second approach was a structural one based on mimicry and grafting onto molecular scaffolds.² These peptides have affinities in the pico- to nano-molar range, functional activity in vivo, making them promising therapeutic leads for checkpoint blockade or potentiation of immunotherapy.

References:

1. Tombling BJ, Lammi C, Lawrence N, Gilding EK, Grazioso G, Craik DJ, Wang CK. Bioactive Cyclization Optimizes the Affinity of a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Peptide Inhibitor. J Med Chem 64:2523-33.
2. Yin H, Zhou X, Huang YH, King GJ, Collins BM, Gao Y, Craik DJ, Wang CK. Rational Design of Potent Peptide Inhibitors of the PD-1:PD-L1 Interactions for Cancer Immunotherapy. J Am Chem Soc 2020 143:18536-18547.