As a pediatric oncologist, I desire to transform outcomes for childhood solid tumors which have not appreciably changed in several decades. Similar to the early days of combination chemotherapy, we expect synergistic immunotherapy to emerge as new standards of care. Before we can usher in this future, the hostile tumor microenvironment (TME) must be reset to facilitate immunotherapy; my lab has achieved this through discovery, development and translation of novel mRNA vaccines.

The Sayour Lab has made advances in fundamental immunobiology while working to extend these into disease treatments. We have revealed that myeloid suppressor cells can be reprogrammed, following mRNA vaccination, to polarize adaptive immunity. Unlike prototypical vaccines, we discovered that mRNA administration route and payload packaging are critical in overcoming tumor mediated immunosuppression. In contrast to current mRNA vaccine designs that rely on payload packaging in nanoparticle cores, my lab has shown that ‘onion-like’ multilamellar RNA lipid-particle aggregates substantially enhance vaccine immunogenicity in murine, canine and first-in-human clinical trials for glioblastoma patients with implications for all cancers.

Our discoveries in cancer biology, immunology, and mRNA development uniquely position us to: 1) define pediatric solid tumor immunobiology; 2) interrogate mechanisms of immune resistance; 2) develop adaptable mRNA vaccine immunotherapies; and 3) translate these advances into first-in-human trials.