The most recent discovery of Dr. Claude Perreault and his team, as explained in Science Translational Medicine magazine
By Krystel Vincent, Research Associate, and Céline Laumont, Ph. D. student, part of Claude Perreault’s laboratory
“Having revealed the existence of several non-mutated tumor-specific antigens in seven human samples, including 4 leukemias, our study provides us with hope that we can thus make this therapy accessible to all types of cancers.”
To present their identity to the immune system, each one of our cells exposes a collection of peptides, also called antigens, generated by the degradation of their proteins. Knowing that the cancer cells produce abnormal proteins, their ID card will be made up of a majority of normal antigens and a few abnormal antigens. Because they are so rare, the abnormal antigens may be missed by the immune system. The goal of the research project was therefore to identify the complete repertoire of the antigens presented exclusively by the cancer cells, for the purpose of developing a vaccine to train our immune system to recognize and eliminate them.
Dr. Perreault’s lab team thought that the antigens presented by our cells for immune surveillance came exclusively from the coding portion of our DNA, meaning from the 2% that are able to produce proteins. The team developed an approach combining genomics, bioinformatics and proteomics, thanks to which it was able to demonstrate that the majority of tumor-specific antigens are produced by the non-coding portion of our DNA! Not only are they large in number, these antigens do not carry any mutations, which considerably increases their chances of being shared by several patients. Along with highlighting the largest repertoire of tumor-specific antigens, the study also brought to light the key factors that can influence the ability of these antigens to induce strong antitumor responses.
Up until now, only cancers with a high mutation rate, such as melanoma, could be treated using a vaccine targeting tumor-specific mutated antigens.
Cancers having very few mutations, such as leukemias, have long been considered being of lesser interest for this type of therapy. In fact, developing therapeutic cancer vaccines targeting this type of antigens would represent an inexpensive way to save lives and would greatly simplify the treatment of this formidable disease by notably limiting the known side effects of chemotherapy.
Noncoding regions are the main source of targetable tumor-specific antigens. Sci. Transl. Med. 10, eaau5516 (2018).
C. M. Laumont, K. Vincent, L. Hesnard, É. Audemard, É. Bonneil, J.-P. Laverdure, P. Gendron, M. Courcelles, M.-P. Hardy, C. Côté, C. Durette, C. St-Pierre, M. Benhammadi, J. Lanoix, S. Vobecky, E. Haddad, S. Lemieux, P. Thibault, C. Perreault
In the media
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