Researchers used a CRISPR-based tool to make "immune cold" prostate cancer vulnerable to immunotherapy in mice. The technology targets and re-lengthens a specific mRNA to restore the MHC-1 complex that immune cells use for recognition. Published in Nature Biomedical Engineering, the study showed this allowed immunotherapy to effectively destroy tumors, offering a new approach for cancers that resist such treatments.
CRISPR RNA targeting technology
- ▪The CRISPR Cas13 system was engineered to attach to a specific section of mRNA, preventing cancer cells from shortening its tail, rather than cutting it
- ▪A detailed analysis of the experimental CRISPR treatment in the study found no detectable off-target effects
- ▪Researchers developed an experimental RNA targeting technology using a CRISPR-based tool to make prostate tumors more vulnerable to an immune attack
Prostate cancer immunotherapy resistance
- ▪A tumor can become immune cold due to the loss of the MHC-1 complex, a molecular signal that helps T cells recognize and kill tumor cells
- ▪Prostate cancer is difficult to treat with immunotherapy because most of its tumors are "immune cold," attracting too few T cells to be effective
Shortened mRNA in tumors
- ▪Shortened mRNAs are more stable and remain active longer, allowing them to produce large amounts of protein without normal cellular controls
- ▪Researchers discovered 12 years ago that many mRNAs in tumor cells, such as in glioblastoma, were shorter than normal
- ▪This mRNA shortening occurs across many cancer types and may help tumors adapt, survive, and escape treatment
MHC-1 complex suppression mechanism
- ▪In prostate cancer, the mRNA that creates the SPSB1 protein is shortened, leading to an overproduction of SPSB1
- ▪A specific protein called SPSB1 destroys the MHC-1 complex in cancer cells
- ▪The overproduction of SPSB1 protein destroys the MHC-1 complex, making the tumor invisible to T cells and rendering immunotherapy futile
Mouse model treatment results
- ▪The treatment restored the MHC-1 complex, causing more immune cells to enter the tumors and destroy cancer cells
- ▪The findings of the study, led by scientists from Duke University School of Medicine, were published in Nature Biomedical Engineering
- ▪In laboratory studies on mice, the CRISPR technology improved the response of prostate tumors to immune checkpoint therapy
- ▪The research was funded by the National Cancer Institute at the National Institutes of Health
Future pancreatic cancer testing
- ▪Researchers plan to investigate if the RNA-targeting approach can work in other immune cold cancers
- ▪A team received pilot funding to test the technology in pancreatic cancer, another tumor type that often responds poorly to immunotherapy
Story comments
Loading comments…