Simultaneous targeting of multiple immunosuppressive genes using Cas13 reduces tumor growth in multiple cancers

In a new study, researchers have developed a new approach that can target several of these tumor-promoting effects at once. They show that this approach is effective in reducing tumor growth in several cancers. Their new findings point to a potential new treatment approach that could benefit more patients than current treatment options.

Traditional therapies target a single molecule in the tumor microenvironment, but this microenvironment is so complex that targeting a single molecule doesn't always work. For example, the best-known of these immunotherapies only benefit 20% to 30% of patients. "

When these therapies don't work, it could be because the molecules they target don't play a major role in an individual's tumor, or it could be because there are other molecules with similar effects that compensate for the loss of the molecule targeted by the treatment. One benefit of Cas13 is its ability to target multiple genes with one molecular package. They identified several genes that can suppress immune responses and developed a Cas13 system that dominates each of them.

When the Cas13 molecular package was delivered to the tumor microenvironment of mice, it was found to silence these immunosuppressive genes, reshape the tumor microenvironment, and enhance anti-tumor immune responses. The result was reduced tumor growth in four cancers: breast cancer, melanoma, pancreatic cancer, and colon cancer.

While more research is needed to further optimize the efficacy and safety of this approach, the technology holds promise as a more general "off-the-shelf" treatment that can also be tailored to specific individuals by swapping out gene targets when necessary.

Reference

• Feifei Zhang et al. Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy. Nature Biotechnology, 2025, doi:10.1038/s41587-024-02535-2.