Little Warrior Commits $150,000 to MSK to Develop Fusion-Derived Cellular Immunotherapies

Continuing our mission to target the oncogenic fusion at the heart of Ewing sarcoma, Little Warrior Foundation has awarded a $150,000, two-year grant to Dr. Swati Jain in the lab of Dr. Luc Morris at Memorial Sloan Kettering Cancer Center (MSK). This project explores a cutting-edge concept in cancer treatment: the use of fusion-derived neoantigens as targets for immunotherapy.

Neoantigens are protein remnants or fragments derived from tumor-specific mutations or fusions that can be made visible to the immune system. This team is investigating which fusion-derived neoantigens in Ewing sarcoma are immunogenic, meaning they can provoke cell death by an immune response. Using advanced computational tools, this research team has identified several promising fusion-derived neoantigens matched to various HLA genotypes (specific to each patient).

The team will validate these fusion-derived neoantigen targets in an HLA-competent mouse model, allowing them to assess in vivo immune responses to these fusion neoantigens. In parallel, they'll use MSK’s extensive Ewing sarcoma tumor bank to determine how common and abundant these neoantigens are across patient samples, using a powerful technique called immunopeptidomics.

To break it down simply, think of HLA genotypes as “display stands” that can scoop into the cell and display these fusion-derived neoantigens on the surface of tumor cells.  This surface display of neoantigens is necessary for immune system recognition. These neoantigens —like those created by EWSR1::FLI1 or other fusions—can serve as “red flags” to the immune system to target these tumors for cell-mediated death by killer T cells

However, sometimes these “red flag” signals aren’t strong enough to overcome the many immune-silencing signals the tumor also displays on the cell surface. And researchers and oncologists need to intervene by boosting a patient’s tumor with a population of T-cells that are personalized and engineered to recognize these fusion-derived neoantigens (red flags).

If successful with these research aims, this approach could lay the foundation for a novel TCR T cell therapy built entirely in-house at MSK’s state-of-the-art Cellular Therapeutics Center. This would bypass the often slow, costly process of finding external biotech partners—an especially critical advantage in rare, pediatric cancers where commercial incentives are limited.

We’re proud to back this transformative research—and to help accelerate the path toward a new kind of precision immunotherapy for Ewing sarcoma warriors everywhere.