Peptide fragments from tumour-related proteins, known as tumour associated antigens, can be displayed on the surface of cancerous cells by MHC molecules and can be recognised by T cells from the patient’s immune system which can kill the cancerous cell. This pathway suggests the possibility of using peptide epitopes in anti-cancer vaccines. Although the approach holds much promise, durable responses in patients are rare. Obstacles include the lack of immunogenicity of peptides, the availability of peptide antigens, and immunosuppression within the tumour microenvironment.
Recent seminal work in the field has shown that the T cell repertoire in responding patients largely recognise patient-specific tumour antigens, known as private or neoantigens, rather than the previously characterised shared antigens (which are much less abundant). As a result, much attention has been directed towards developing vaccines that target these patient-specific antigens.
We have developed a powerful peptide-based vaccine that consists of peptide antigens linked through a protease-cleavable linker to a glycolipid adjuvant which stimulates NKT cells. We chemically synthesized a previously reported [1] set of 21 neoantigens and chemically conjugated them to the adjuvant using oxime ligation. Durable responses in aggressive murine tumour models were observed when the neoantigen cancer vaccine was combined with other forms of immunotherapy.