Prostate cancer often hides from the body’s defense system, making it hard for immunotherapy to work. A new RNA‑editing method based on CRISPR can change that.
Most prostate tumors are called “immune‑cold” because they attract very few T‑cells, the soldiers that kill cancer. Without enough T‑cells, checkpoint drugs have little effect.
Researchers used a CRISPR‑Cas13 tool to fix a shortened messenger RNA (mRNA) that makes a protein named SPSB1. In prostate cancer, this mRNA is too short, so the cell makes too much SPSB1, which destroys the MHC‑1 complex that shows cancer cells to T‑cells.
By attaching the CRISPR system to the mRNA, the scientists prevented it from being trimmed. The mRNA stayed at its normal length, producing less SPSB1. As a result, the MHC‑1 complex returned, and T‑cells could recognize the tumor.
When mice with prostate tumors received this treatment together with checkpoint therapy, many more immune cells entered the tumor and killed the cancer cells. The study found no off‑target damage from the CRISPR tool.
“We showed that making the mRNA longer can revive the immune signal and improve therapy,” said lead researcher Dr. Wagner.
The team now wants to test the same approach in other “cold” cancers, such as pancreatic cancer, where immunotherapy also fails.
This work was supported by the National Cancer Institute.