![Moditope®](/Data/Sites/1/media/img/Moditope-hdr.png)
The Moditope® platform is based on exploiting the normal immune responses that remove stressed cells and represents a unique class of potent vaccines that is characterised by the induction of CD4 cytotoxic T cells. The nature of tumours means that most cancer cells live in stressful conditions that are often hypoxic and nutrient deficient. To survive in this environment, cancer cells often undergo autophagy, a process that allows cells to generate energy from the digestion of intracellular proteins and organelles. During this process stress-induced post-translational modifications (siPTMs) and proteolytic cleavage occurs resulting in the generation of peptides which can be presented on the cell surface complexed with major histocompatibility class II (MHC-II) molecules for recognition by T cells. However, cancer cells do not normally express MHC class II on their cell surface unless this is induced by inflammation. Examples of such modifications are citrullination, an enzyme-based conversion of arginine to citrulline, and homocitrullination (or carbamylation), in which lysine residues are converted to homocitrulline.
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After vaccination with citrullinated or homocitrullinated peptides, the peptides are taken up by antigen presenting cells (APCs), such as dendritic cells, which process the peptides and present them to CD4 T cells. As these CD4 T cells infiltrate into the tumour microenvironment, they encounter modified peptides expressed on the surface of APCs and, as a result, the CD4 T cells become activated and secrete interferon-gamma (IFNγ) which induces inflammation and the up-regulation of MHC class II. The activated CD4 T cells can then see the modified peptides presented on MHC class II and directly kill the tumour cells.
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Scancell currently has two Moditope® vaccines in clinical and preclinical development:
- Modi-1, a vaccine based on citrullinated peptides for the treatment of solid tumours including triple negative breast, ovarian, renal and head & neck cancers;
- Modi-2, utilises homocitrullinated peptides to address different cancer indications to Modi-1, including tumours with a particularly immunosuppressive environment.