In lab and mouse experiments, UC San Diego School of Medicine researchers developed a method to leverage B cells to manufacture and secrete tumor-suppressing microRNAs.
Cancer immunotherapy — efforts to better arm a patient’s own immune system to attack tumors — has shown great potential for treating some cancers. Yet immunotherapy doesn’t work for everyone, and some types of treatment can cause serious side effects.
In a new approach, researchers at University of California San Diego School of Medicine are turning B cells, best known for producing antibodies, into factories that assemble and secrete vesicles or sacs containing microRNAs. Once internalized by cancer cells, these small pieces of genetic material dampen a gene that spurs tumor growth. In mice, breast tumors treated with this approach were fewer and significantly smaller than in untreated tumors.
The study is published in the December 4 issue of Scientific Reports.
“Once further developed, we envision this method could be used in situations where other forms of immunotherapy don’t work,” said senior author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and head of the Laboratory of Immunology at UC San Diego Moores Cancer Center. “The advantages are that this type of treatment is localized, meaning potentially fewer side effects. It’s long-lasting, so a patient might not need frequent injections or infusions. And it would likely work against a number of different tumor types, including breast cancer, ovarian cancer, gastric cancer, pancreatic cancer and hepatocellular carcinoma.”
MicroRNAs don’t encode proteins. Instead, microRNAs bind messenger RNAs that do encode proteins, inhibiting their translation or hastening their degradation. Normal cells use microRNAs to help fine-tune which genes are dialed up or down at different times. MicroRNAs tend to be less active in cancer cells, which can allow growth-related proteins to run wild.
In this study, Zanetti and team used miR-335, a microRNA that specifically dampens SOX4, a transcription factor that promotes tumor growth. They added a miR-335 precursor to B cells in the lab. Once inside, through a naturally occurring process, the cells convert the precursor into mature, active miR-335 and package it into vesicles, small, membrane-coated sacs that bud off from the cell. Each B cell can produce 100,000 miR-335-containing vesicles per day — enough to treat 10 cancer cells.