RE: Moditope patent - homocitrullinated peptides19 Mar 2020 17:46
Surprisingly, the inventors have found that certain homocitrullinated epitopes are associated with tumours and consequently can be used to raise an immune response against such tumours. The inventors have identified carbamylation (or homocitrullination), which can occur on specific proteins, including but not restricted to vimentin, ALDOA, cytokeratin 8, immunoglobulin binding protein, nucleophosmin (NPM), oenolase, b-catenin and HSP60, that leads to strong T cell immunity. Homocitrulline peptide vaccination stimulated specific CD4 and CD8 responses that mediated efficient tumour therapy. As CD4 and CD8 T cells recognise peptides presented by MHC-II and MHC-I molecules respectively, the carbamylated proteins need to be processed and access the MHC class I or class II pathways. This could be within MPO expressing antigen presenting cells which could the present the carbamylated epitopes on MHC-I or MHC-II to activated CD8 or CD4 T cells. These cells could then mediate a bystander anti-tumour effect by releasing cytotoxic cytokines which can have a cytostatic or cytotoxic effect on the tumour cells and/or recruit other immune effectors cell such as CD8 T cells (Hung et al. 1998).
a lot to study