CRISPR restores immune signal in prostate cancer
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- Duke University School of Medicine scientists led a collaborative team that built an RNA-based CRISPR Cas13 system designed not to cut but to bind a specific section of mRNA, blocking cancer cells from shortening the molecule's tail and forcing it back to its normal length.
- The CRISPR treatment restored the MHC-1 complex on prostate cancer cells — the molecular 'magnet' that attracts T cells — and improved response to immune checkpoint therapy in mice, with more immune cells entering tumors and attacking cancer cells.
- The protein SPSB1 destroys the MHC-1 complex, and in prostate cancer the mRNA carrying its instructions is shortened, producing more SPSB1 protein and making tumors 'immune cold'; no detectable off-target effects were found in detailed analysis of the CRISPR treatment.
- Eric J. Wagner, PhD, co-author from University of Rochester Medicine and professor of Biochemistry and Biophysics, said the tool could be used with existing immunotherapies in prostate and other immune-cold tumor types.
- Wagner's team discovered the mRNA-shortening phenomenon 12 years ago while studying glioblastoma and has now received pilot funding from Wilmot Cancer Institute and Roswell Park Comprehensive Cancer Center to test the technology in pancreatic cancer.
- The findings were published in Nature Biomedical Engineering and funded by the National Cancer Institute at the National Institutes of Health.
Why it matters: Prostate cancer has historically resisted immunotherapy because its tumors attract too few T cells, leaving patients without immune-based options. This preclinical work introduces a novel mechanism — re-lengthening shortened tumor mRNA to restore MHC-1 and immune visibility — and if it translates, it could extend checkpoint therapy to prostate cancer and other immunologically silent tumors like pancreatic.
