Design and optimization of a novel proteomimetic polymer nanoplatform for the co-delivery of antigens with adjuvants

Newswise — We describe here a novel nanoplatform called the Protein-Like Polymer (PLP) with unique characteristics allowing for sustained delivery of tumor antigens in conjunction with STING agonists.

Methods

A library of PLP formulations were synthesized via ROMP and characterized. Cell uptake/functional assays were conducted with payload-specific T Cells. Ability of PLPs to co-deliver adjuvants was tested by electrostatically coupling 2'3' CGAMP, forming stable nanostructures.

Results

Conjugating antigens to the polymer backbone using a cleavable disulfide linkage (reduces in APCs) resulted in increased endosomal localization and T cell proliferation/activation. Incorporating OEG side chains reduced enzymatic degradation while increasing immunogenicity and APC uptake. Increasing the density of side chains further improved vaccine efficacy and resistance to proteolysis. Antigen-PLP conjugates is effective only when paired with cells from their cognate system, demonstrating payload-specificity. Mice bearing established B16F10 tumors treated with gp100-PLPs resulted in increased survival time and reduced tumor burden with corresponding changes in immune cell profiles. Notably, STING-PLP complexes showed significantly smaller tumors at day 14 and allowed for subcutaneous administration of 2'3' CGAMP. Studies looking at multiplexing pools of neoantigens onto one PLP and generation of immunological memory are ongoing.

Conclusion

The modularity of the PLP platform allows for complex nano-architectures including systems capable of delivering challenging compounds, ie small molecule STING agonists, subcutaneously through electrostatic coupling, highlighting its potential to revolutionize cancer vaccinology.