Mutations in Cancer Cells Enhance Effectiveness of Cell Therapies, Study Shows
Cancer cells, with their ability to survive and thrive despite mutations, may hold the key to improving cell therapies for cancer treatment. A recent study conducted on mice has shown that mutations found in cancerous T cells can enhance the effectiveness of chimeric antigen receptor (CAR) T cell therapies, which are already used to treat certain types of blood cancer.
CAR-T cell therapies involve collecting T cells from individuals with cancer and modifying them to express CAR proteins. These proteins enable the T cells to identify and destroy cancer cells. While CAR-T cell therapies have been successful in treating blood cancers, scientists have been uncertain about their efficacy against solid tumors like breast and lung cancers.
To address this challenge, researchers led by immunologist Kole Roybal from the University of California, San Francisco, incorporated 71 mutations found in cancerous T cells into CAR T cells. Among these mutations, one stood out as particularly effective in enhancing T-cell function. The CAR T cells carrying a mutation known as CARD11-PIK3R3 showed excellent infiltration into tumors and demonstrated long-lasting cancer-killing activity.
The team then tested these mutation-enhanced CAR T cells on mice with both blood and solid cancers. Even with a significantly smaller number of cells (20,000 instead of the usual one million), the mutated CAR T cells successfully eradicated the tumors. This finding is promising as it suggests that fewer cells may be needed for effective treatment.
While there is a concern that the supercharged cells may transform into cancers themselves, the animal data did not raise any safety concerns. The CARD11-PIK3R3 mutation appears to only amplify the edited T cells’ activity when cancer cells are present, reducing the risk of rogue immune cells.
The researchers, Jaehyuk Choi and Kole Roybal, have co-founded Moonlight Bio in Seattle, Washington, with the aim of advancing these mutation-enhanced CAR T cells for use in human cancer patients. They anticipate that clinical trials could begin in two to three years. Additionally, this study opens up opportunities to explore other cancer mutations that could further improve T-cell therapies.
Experts in the field are optimistic about the findings. Madeleine Duvic, a dermatologist and cancer researcher at the MD Anderson Cancer Center, describes the study as a “beautiful piece of work” that paves the way for better CAR-T therapies in the future. Nick Restifo, a cell-therapy researcher and chief scientist of Marble Therapeutics, commends the study for its impressive results with a small number of cells.
The potential of mutation-enhanced CAR T cell therapies is significant. By harnessing the power of cancer cells’ mutations, researchers may be able to develop more effective treatments for various types of cancer. As scientists continue to explore and understand the complexities of cancer cells, the future of cell therapies looks promising.
