Oncolytic measles virotherapy encoding the neutrophil-activating protein is effective in synovial sarcoma

Synovial sarcoma (SS) is an aggressive mesenchymal malignancy that is refractory to treatment with immune checkpoint inhibitor-based therapy. We investigated the infiltrating T cell immune status in archived patient samples and tested the efficacy of an oncolytic measles virus (MV) encoding the secretory form of the neutrophil-activating protein (s-NAP) in SS. To assess T cell infiltration, we performed T cell receptor (TCR) sequencing on archived formalin-fixed, paraffin-embedded specimens, comparing SS with undifferentiated pleomorphic sarcoma (UPS), a highly immunogenic sarcoma. Patients with SS had significantly lower T cell infiltration, reduced clonality, and higher TCR diversity than those with UPS. No differences were observed in the T cell repertoire between monophasic and biphasic SS or between primary and metastatic SS samples. Oncolytic MV-s-NAP infection of validated monophasic and biphasic SS cell lines demonstrated dose-dependent killing in all cell lines tested and a significant increase in proinflammatory markers compared to untreated controls. Additionally, repeated intratumoral injections of MV-s-NAP in an SYO-1 SS xenograft model demonstrated significant anti-tumor effects <i>in vivo</i>. These findings suggest that oncolytic virotherapy using MV-s-NAP, a potent Toll-like receptor agonist, may offer a promising immunovirotherapy approach for patients with recurrent or disseminated SS.