A “smart bomb” may one day save the lives of kids with the most common and deadly form of childhood cancer.
A new study shows how the approach under development could help children with B-lineage acute lymphoblastic leukemia (ALL) who have relapsed after initial chemotherapy and face a less than 20 percent chance of longterm survival.
“We knew that we could kill chemotherapy-resistant leukemia cells if we only knew what made them so resistant. Once we determined the mechanism, the next step was obvious—to rationally design a drug that would take out that specific target,” says Fatih Uckun, professor of research pediatrics at the Keck School of Medicine at University of Southern California.
The target of the “smart bomb” is a defective gene that results in the production of an abnormal form of the protein CD22, which causes cancer stem cells to proliferate and resist chemotherapy.
The defective gene can thwart standard treatments for recurrent disease—including “supralethal” chemotherapy, total-body irradiation (TBI), and bone marrow transplantation.
Small but powerful
Researchers designed synthetic pieces of genetic material, called RNAi, with the capability to shut down this defective gene.
Then Uckun joined forces with Jianjun Cheng, associate professor of materials science and engineering at the University of Illinois at Urbana-Champaign. Cheng’s team engineered a small subunit of protein, called a polypeptide, to function as a delivery system to send the RNAi to its target.
The resulting “smart bomb” has a diameter of only 100 nanometers, making it one of the new generation of nanomedicines that can target disease at a molecular level.
“The goal is to translate our recent research discoveries in nanotechnology and biotherapy into effective patient-tailored treatment programs for the most common form of childhood cancer,” Uckun says.
USC Stem Cell’s Regenerative Medicine Initiative (RMI) funded the research that is published in the journal EBioMedicine.