Multivalent Nanomedicine to Treat High-Risk Pediatric Solid Tumors
Lay Summary: Current therapy of high-risk pediatric solid tumors like neuroblastoma (NB) and sarcomas requires extremely intense treatment. However, cure rates are <50%, and there are significant long-term side effects in survivors. Targeted delivery of anticancer agents using nanomedicines can dramatically improve efficacy and reduce systemic toxicity. We have packaged SN38, the active product of Irinotecan, in small packets called nanoparticles (NPs). Because nanomedicines can easily pass through the leaky blood vessels of tumors, but not most normal blood vessels, much more drug gets to the tumor and much less to the rest of the body. This treatment “cured” most mice in an NB model using only a fraction of the standard irinotecan dose, which cured none.
In this proposal, we will test a novel drug called SN22, which is related to SN38 but makes it harder for the cancer cells to pump out of the cell and eliminate from the body. We have developed a novel nanomedicine delivery system that carries four copies of SN22. We will assess antitumor effects as well as toxicity in mouse models of NB. We are also testing this SN22 formulation in mouse models of Ewing sarcoma, rhabdomyosarcoma and osteosarcoma to show efficacy in other pediatric solid tumors. The successful completion of these studies will inform a phase 1 clinical trial for recurrent or refractory solid tumors children.