A measles virus encoding a CD19/CD3 bispecific T cell engager shows enhanced preclinical anti-BCP-ALL efficacy without significant toxicity.

Children with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) continue to face relapse and treatment resistance, emphasizing the urgent need for novel therapeutic strategies. In this study, we developed and characterized a recombinant oncolytic measles virus (MV-Blina) engineered to locally secrete a bispecific T cell engager (bsTE) targeting CD19 and CD3 (secBlina) to enhance antitumor immunity while minimizing systemic toxicity. MV-Blina demonstrated superior replication kinetics and cytotoxicity in vitro compared to the parental MV-Edm strain. MV-Blina infected ALL cells, secreted functional secBlina capable of engaging and activating T cells, leading to selective leukemia cell death. In in vitro and in vivo models, including patient-derived xenografts, MV-Blina demonstrated an additive yet heterogeneous anti-leukemic effect, with significant survival benefits and reduced CNS leukemic burden in MV-Blina-treated mice. Importantly, MV-Blina did not induce either short- or long-term toxicity in in vitro neuronal models encompassing PBMCs, nor in immunocompromised CD46 transgenic mice, even under additional immunosuppression. Collectively, these findings support further investigations of MV-Blina as a potential treatment for patients with relapsed or refractory BCP-ALL.