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.
Project Goal: 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.
Project Update 2022: We used three different types of mouse models of high-risk neuroblastoma, and we cured most or all mice with just four weekly injections of our novel nano medicine, whereas the conventional agent cured none, even at the highest tolerated doses. We also had similar effects on mouse models of rhabdomyosarcoma and Ewing sarcoma. This shows that the efficacy of this SN22 nano medicine is not restricted to neuroblastoma, and perhaps could be used in virtually any solid tumor in children or adults. The preclinical data we provided helped PEEL Therapeutics to develop our agent as PEEL-224 and have led to a Phase 1 clinical trial in adults with gastrointestinal cancers and sarcomas, which has just begun. Once they have sufficient dosing and toxicity information, this will lead to a pediatric phase 1 trial in children and adolescents with recurrent or resistant solid tumors.
