Hepatoblastoma (HB) is the most frequent pediatric form of liver cancer, generally arising in young children (<3yo). Despite being a rare tumor (1.8 in 1,000,000 children/year), HB rates are on the rise and therapeutic options are limited to chemotherapy. Chemotherapy (i.e. cisplatin) is given to patients without any consideration to a specific mutation within tumors and toxicity is significant. Here we seek to advance a novel therapeutic candidate for HB that has been optimized to selectively kill cancer cells with specific mutations, while sparing normal hepatocites.

Cancer is the leading cause of death by a disease in children ages 0-19 years old. Whereas cure rates for pediatric hematologic malignancies as a class can reach 90% or more, solid tumor cures have historically lagged and contribute disproportionately to the cancer death rate in children. A common mechanism among relapsed and treatment-resistant pediatric solid tumors is a combination of errant signaling that drives cancer cell proliferation and blocks cancer cell death. Thus, multiagent treatment that addresses multiple cancer-causing pathways is required.

Germ cell tumors (GCTs) are rare tumors that occur in various locations including the brain. Intracranial GCTs (IGCTs) can be divided into germinomas and nongerminomatous germ cell tumors (NGGCTs) with NGGCTs further divided into five subtypes. IGCTs can be treated with various combinations of chemotherapy and radiotherapy with the germinomas having better response than NGGCTs. Because these tumors are found deep in the brain, obtaining a biopsy for diagnosis is very challenging and risky.

Lay Summary: Blood stem cell transplantation can cure acute lymphoblastic leukemia (ALL) in children who have no other remaining treatment options. Traditionally, this has not been available for all patients because of the need for stem cell donors that are compatible (matched). Over the last decade, a novel procedure has been developed in which immune cells - called T cells - that could attack patient cells in case of a mismatched transplant, are removed from the graft before the infusion (αβ haplo-HSCT).

Lay Summary: Pediatric leukemia remains the second leading cause of cancer death in children. While outcomes for newly diagnosed patients have dramatically improved in the last several decades, response rates for relapsed ALL remain <50%. Chimeric antigen receptor (CAR) T cells are immune cells that are taken out of the body and genetically changed to attack cancer cells. CAR T cells are typically made from the patient’s own immune cells.