SupraCODE · Spatial control of antigen-encoded supramolecular copolymers for robust T-cell activation against cancer

Nature uses a complex chemical language between cells and their environment to sustain life. T-cells, critical players of the immune system, constantly communicate and respond to environmental signals through cell-fate decisions to protect against pathogens. Their function in the immune system is of particular interest for cancer immunotherapy where their activation and expansion can be harnessed to kill cancer cells. Low affinity CD 8+ T-cells are attractive because of their memory to prolong the duration of therapy, but they are challenging to expand unlike their high affinity counterparts. In this proposal, I will explore the multimerization of tumor-associated antigens (TAAs) through the H2-Kb-OVA peptide complex on supramolecular polymer scaffolds to potentiate the activation and expansion of low-affinity CD8+ T-cells. I will develop monomers that undergo kinetically controlled supramolecular polymerization in water and explore the potential to prepare block copolymers by modulating the monomer design with respect to hydrogen bonding and hydrophobicity. Supramolecular block copolymers will be engineered with domains of distinct sizes at the nanoscale to enable control over the TAA presentation with respect to spacing and density. Additionally, the effect of modulating OVA peptide sequence Using a library of H2-Kb-OVA peptide complex outfitted supramolecular block copolymers with various peptide sequences I will map the potential for activation and expansion of low affinity CD 8+ T-cells. Importantly, the major aim of this proposal is to develop strategies to prepare supramolecular block copolymers in water with bioactive units to broaden the application space of this materials class in the biological field.