The post-translational conversion of arginine residues to citrulline by peptidylarginine deiminase (PAD) enzymes requires millimolar concentrations of calcium. This can occur during apoptosis leading to precipitation of proteins and stimulation of CD4 and antibody responses which are associated with autoimmune diseases such as rheumatoid arthritis (RA). Citrullination has also been shown to occur as a result of a degradation and recycling process called autophagy that is induced in stressed cells. As such autophagy and citrullination could be a method for alerting the immune response to any stressed cell including tumour cells. Peptide epitopes from these modified epitopes are presented on MHC-II and stimulate CD4 T cell responses. To this end, we have shown that stress-induced citrullinated peptide epitopes induce potent, cytotoxic CD4 T cell-mediated, anti-tumour responses that could constitute a new class of cancer treatment.
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Lindy Durrant (LD) is a Prof of Cancer Immunotherapy in the Division of Cancer and Stem cells (CSC) and CSO of Scancell holdings plc.. LD’s research has focused on developing mAbs and vaccines for cancer therapy and she has 147 peer reviewed publications Lindy is the inventor on 66 patents 55 of which have been awarded. She currently has a mAb and a cancer vaccine in phase I/II clinical trials.