CRISPR makes prostate cancer vulnerable to immunotherapy - ScienceDaily

What the report says

ScienceDaily, citing materials from University of Rochester Medicine, reported July 26 that researchers have developed an experimental CRISPR-based approach that made prostate cancer tumors more responsive to immunotherapy in mouse studies. The findings, published in Nature Biomedical Engineering, involve an RNA-targeting system intended to make tumor cells easier for immune cells to recognize and attack.

The report says many prostate tumors are considered “immune cold,” meaning they draw too few T cells for immune checkpoint treatments to work well. Researchers traced part of that immune evasion to shortened messenger RNA linked to SPSB1, a protein that reduces the MHC-I complex, which helps T cells identify abnormal cells. When MHC-I is depleted, tumors can become harder for the immune system to detect.

A collaborative team led by Duke University School of Medicine scientists used a CRISPR Cas13 system designed to bind RNA rather than cut it. By keeping the SPSB1 messenger RNA in a longer form, the tool reduced SPSB1 production and allowed MHC-I levels to recover, according to the ScienceDaily account. In mice, that shift brought more immune cells into prostate tumors and improved the effect of immune checkpoint therapy. The researchers reported no detectable off-target effects in their analysis of the experimental treatment.

The work remains preclinical, so it has not yet been shown to be safe or effective in people. Still, the approach matters because prostate cancer has generally responded less well to immunotherapy than some other cancers. University of Rochester researcher Eric J. Wagner and colleagues plan to examine whether similar RNA engineering could help other immune-cold tumors, including pancreatic cancer. The research was funded by the National Cancer Institute at the National Institutes of Health.