Researchers have developed a synthetic DNA molecule intended to jump start the immune system, allowing it to mount an attack against genetically distinct types of prostate cancer. The system was developed by researchers from the cancer center and research institution, City of Hope, and details of the pre-clinical trail were published in the journal Clinical Cancer Research.
The strategy works by eliminating STAT3, a transcription factor that enables tumors to become resistant to existing therapies, and activating the TLR9 danger sensor. The researchers programmed a small bit of DNA that temporarily lifts the defense shield of tumors, allowing the immune system to react. The system was successfully tested in human cell and mouse models of various prostate cancers.
"We desperately need new strategies for late-stage prostate cancers, which thus far have resisted emerging immunotherapies," said Marcin Kortylewski, Ph.D., associate professor in the Department of Immuno-Oncology at City of Hope and co-senior author of the study.
The new type of DNA is called CpG-STAT3ASO delivers a one-two punch to treat metastatic tumors resistant to pharmacological therapies—a synthetic molecule with just STAT3 or TLR9 was not as effective at killing prostate cancer as the combination.
The researchers believe this DNA molecule could someday be used for therapeutic vaccination against metastatic prostate cancer, but more preclinical research into the dug’s pharmacological properties is needed before that can occur.
Image: DNA drug (CpG-STAT3 antisense, red) is penetrating human prostate cancer cells within 15 minutes of exposure (CpG-STAT3 antisense, red; intracellular vesicles, green). Image courtesy of City of Hope.