WT1-targeting immunotherapy in children with refractory cancer

Abstract

Wilms tumor 1 (WT1) was considered as a high-priority antigen target for cancer immunotherapy because of its high immunogenicity and oncogenicity, as well as its expression in the majority of pediatric hematologic malignancies and solid tumors. We reported previously the cases of recurrent rhabdomyosarcoma patients. A female patient received WT1 peptide vaccination after radiation therapy and became well after the WT1 peptide vaccine treatment. We reported previously on a male pediatric patient with relapsed diffuse midline glioma, whose H3.3K27M mutation was demonstrated by immunohistochemistry. He exhibited an encouraging clinical evolution during WT1 peptide vaccination as manifested by a stable disease, improved clinical manifestations, steroid dose reductions, a WT1-specific immune response, and a good safety profile. In pediatric refractory patients with leukemia, we performed a phase II clinical study of immunotherapy targeting the WT1 protein. We were able to show that WT1 vaccination is safe and can induce a WT1-specific immune response. Therefore, this immunotherapy is a potentially promising therapeutic modality for refractory pediatric cancer. We created a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying the WT1 protein. Orally administered B. longum significantly inhibited WT1-expressing tumor growth and led to protracted survival in mice. We have clarified the mechanism of efficacy of this oral vaccine, which is expected to be effective without severe adverse events and pain for pediatric patients.