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

## TL;DR

A modified measles virus that activates neutrophils shows promise in treating synovial sarcoma, a cancer resistant to standard immunotherapy.

## Contribution

The study introduces an oncolytic measles virus encoding s-NAP as a novel immunovirotherapy for synovial sarcoma.

## Key findings

- Synovial sarcoma shows low T cell infiltration and diversity compared to other sarcomas.
- MV-s-NAP effectively kills synovial sarcoma cells and increases proinflammatory markers.
- MV-s-NAP injections in a synovial sarcoma xenograft model resulted in significant anti-tumor effects.

## Abstract

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 in vivo. 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.

Robinson and colleagues demonstrate that monophasic and biphasic synovial sarcomas exhibit low T cell infiltration and diversity, contributing to its immunotherapy resistance. They show that oncolytic measles virus encoding s-NAP (MV-s-NAP) exhibits significant anti-tumor effects, highlighting a promising immunovirotherapy approach for recurrent or disseminated synovial sarcoma.