Montréal – Researchers at CHU Sainte-Justine have identified new targets on the surface of cancer cells that could be exploited by future, highly targeted immunotherapies, opening up new possibilities for treatment. The findings, announced on , represent a significant step forward in the fight against pediatric cancers.
A novel computational tool developed by a team at CHU Sainte-Justine, called ProteoFusioNEO, allowed for the analysis of transcriptomes from over 5,100 children with various pediatric cancers, as well as 935 cell lines. This extensive analysis led to the identification of neoantigens – small fragments of abnormal proteins resulting from gene fusions – present on the surface of cancer cells.
“What characterizes pediatric cancers is a rather unique genetic signature,” explained Isabelle Sirois, head of the Proteomics and Immunopeptidomics Platform at CHU Sainte-Justine. “We call them gene fusions, which are pieces of genes that fuse together and create super genes (…) that alone can induce cancer. So, when we need to find new therapeutic targets that are unique to cancer cells, they have this signature.”
The development of these highly targeted immunotherapies offers the hope of specifically attacking cancer cells without harming healthy cells. However, this requires presenting the immune system with targets that are found only on the diseased cells. This represents where the identification of these neoantigens becomes crucial.
At the heart of this therapeutic promise lies immunopeptidomics, an approach that identifies small protein fragments on the cell surface. 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 must get rid of its protein waste more or less continuously,” Sirois explained. “These wastes are loaded onto molecules that bring them to the cell surface, and that serves as a molecular flag for the immune system.”
In other words, she clarified, the immune system “monitors the surface to see if there are small pieces of protein that shouldn’t be there.”
Not all neoantigens represent the same therapeutic potential, but some are particularly interesting because they are extremely specific and distinct from peptides associated with normal proteins in the body, making them prime targets for precision immunotherapies.
These developments pave the way for the potential development of mRNA vaccines that would train the immune system to recognize neoantigens resulting from gene fusions, or therapeutic antibodies capable of either recruiting the immune system’s killer cells to the tumor or acting as Trojan horses, delivering chemotherapy directly to the heart of the cancer cells.
“We’re going to do exactly the same thing as we did with the mRNA vaccines during COVID,” Sirois said. “But instead of giving a virus sequence, we’re going to put the sequences of the molecular flags that will train the immune system to kill tumor cells in the patient.”
One of the main advantages of their technique, she emphasized, is that it allows for the determination of the quantity of targets on the cell surface, which will guide the development of immunotherapies. Some immunotherapies, Sirois noted, need “a lot of targets, and others a little less.”
The research builds on growing momentum in personalized cancer treatments. A study published in in Nature highlighted the constraints of current immunotherapy approaches for pediatric solid and brain tumors due to limited targetable antigens, and identified 2933 exons in 157 genes with high cancer specificity. This work underscores the importance of identifying these unique cancer-specific targets.
advancements in personalized mRNA cancer vaccines are also being explored elsewhere. Providence Therapeutics announced on , a world-first clinical trial evaluating personalized mRNA cancer vaccines for children with advanced and treatment-resistant brain tumors, beginning in March 2026 across seven pediatric hospitals in Australia. This trial, PaedNEO-VAX, will create vaccines tailored to each patient’s tumor biology.
UCSF is also a national leader in shifting the focus of pediatric cancer treatment to the genetic makeup of individual tumors. Through the Pediatric Precision Cancer Medicine Program, UCSF pediatric oncologists are using advanced sequencing technologies to identify specific mutations driving a child’s cancer, leading to more effective and less toxic treatments. As one parent shared, this approach allowed for a pivot to an effective treatment plan after initial chemotherapy proved ineffective due to genetic resistance.
“There are really new possibilities for treatment, apart from chemotherapy that we’ve been using for 70 years for pediatric cancers,” Sirois concluded. “It’s very promising.”
