Submission of the Week
Genomics & Genetics
T cell receptors (TCRs) are extremely specific in their ability to recognise peptide antigen presented by diseased cells. T cells are naturally selected to not recognise self peptide antigens as potential danger. As tumours are derived from our own cells, the peptide antigens often presented by malignant cells do not elicit T cell activation; this establishes immune tolerance and protects the tumour from T cell directed killing. However, tumour associated antigens have been discovered, along with tumour specific T cells isolated from lymphocytes that have infiltrated the tumour tissue.
One type of adoptive cell transfer uses genetically engineered TCRs to target tumour associated antigens, re-directing a patient’s immune system and overcoming tumour immune tolerance. T cells are isolated from the patient’s tumour and engineered ex vivo with a viral vector encoding the tumour specific TCR trans-gene, then infused back into the patient.
Engineered TCRs may also recognise similar peptide antigens expressed in healthy tissue. The authors of this poster present a novel webserver, Expitope, that allows users to find all proteins with an exact match to the peptide antigen of interest. In addition it generates approximate matches, that may have the potential to cause TCR cross-reactivity. The authors apply their webserver to an example from a previous clinical trial that used TCRs engineered against MAGE-3 tumour associated antigen. Unknowingly, engineered TCRs could also recognise a similar peptide antigen expressed in healthy cardiac tissue. Authors demonstrate how this tool can be used to exclude similar antigen targets, helping to prevent fatal effects of engineered TCR cross-reactivity.
K Haase, S Raffegerst, DJ Schendel, D Frishman Based on: European Conference on Computational Biology 2014
Based on: European Conference on Computational Biology 2014, Poster ID:1096788
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