Montreal researchers found new targets on cancer cell surfaces that could be used by future ultra-targeted immunotherapies, opening up new treatment possibilities. A new computer tool developed by a team at CHU Sainte-Justine, ProteoFusioNEO, has made it possible to analyze the transcriptomes of more than 5,100 children with various pediatric cancers, as well as 935 cell lines. This led to the identification, on the surface of cancer cells, of neoantigens — small fragments of abnormal proteins resulting from gene fusions. “What characterizes pediatric cancers is a fairly unique genetic signature,” said Isabelle Sirois, head of the Proteomics and Immunopeptidomics Platform at CHU Sainte-Justine. “These are called fusion genes, which are pieces of genes that fuse together and create super genes...that can induce cancer on their own. So when we need to find new therapeutic targets that are unique to cancer cells, they have that signature.” New ultra-targeted immunotherapies offer hope that one day medicine will be able to attack cancer cells specifically, without harming healthy cells. But to do so, the immune system must be presented with targets that are found only on diseased cells. At the heart of this therapeutic promise is immunopeptidomics, an approach that identifies small protein fragments on the surface of cells. Mass spectrometry and computational tools developed as part of a new study published in the journal iScience were able to predict and then confirm that neoantigens resulting from gene fusions are indeed presented on the surface of cancer cells. “The cell has to get rid of its protein waste more or less continuously,” said Sirois. “This waste is loaded onto molecules that carry it to the cell surface, where it acts as a molecular flag for the immune system.” In other words, she explained, the immune system “monitors the surface for small pieces of protein that are not supposed to be there.” However, not all neoantigens have the same therapeutic potential. But, some are particularly interesting because they are extremely specific and distinct from peptides associated with the body’s normal proteins, making them prime targets for precision immunotherapies, according to a news release. These developments pave the way for the development of messenger RNA vaccines that would train the immune system to recognize neoantigens resulting from gene fusions, therapeutic antibodies capable of either recruiting the immune system’s killer cells to the tumor or acting as Trojan horses by delivering chemotherapy directly to the heart of cancer cells. “We’re going to do exactly the same thing we did with messenger RNA vaccines during COVID,” said Sirois. “But instead of giving a virus sequence, we’re going to put in the sequences of molecular flags that will train the immune system to kill tumor cells in the patient.” One of the main advantages of their technique, she said, is that it allows them to determine the number of targets on the surface of cells, which will guide the development of immunotherapies. Some immunotherapies, said Sirois, need “a lot of targets, and others a little less.” “There are really new treatment possibilities, apart from the chemotherapy that has been used for 70 years for pediatric cancers,” she concluded. “It’s very promising.” This report by The Canadian Press was first published Feb. 15, 2026. Jean-Benoit Legault, The Canadian Press
