Personalized immunotherapies are a promising approach to treating cancer. An interdisciplinary team from Tübingen has been following a patient with Ewing sarcoma for many months. The results have now been published in the journal npj Precision Oncology.
Ewing sarcoma is a rare, aggressive cancer that primarily affects children and young adults and most often arises in bone. The majority of Ewing sarcomas carry the genetic driver fusion EWSR1–FLI1. Because this alteration occurs exclusively in tumor cells, it offers an ideal, tumor-specific target for immunotherapy. The Tübingen team developed a vaccine made up of four overlapping peptides precisely tailored to this gene fusion. Following standard treatment (chemotherapy, surgery, and radiation), the vaccine was administered to an adult patient with metastatic Ewing sarcoma. Over the course of 26 months, the patient received a total of 23 vaccinations. The patient is doing clinically very well. Compared with conventional therapies, the vaccine was very well tolerated and caused no side effects.
Robust, long-lasting peptide-specific T-cell response
Whether a vaccine actually triggers a specific immune reaction can only be confirmed in the laboratory. Using in vitro peptide stimulation and intracellular cytokine staining, the researchers were able to demonstrate a sustained, specific immune response in the patient.
A promising first step
The authors interpret the temporal correlation between the sustained immune response and stable disease course as an encouraging signal for the feasibility, safety, and immunogenicity of fusion-derived peptide vaccines, and advocate for evaluating this approach in controlled clinical trials. Since this is based on the observation of a single patient, a causal link between the vaccination and disease stability cannot be conclusively established — but the data provide important early indications supporting further investigation of this approach.