New technology makes cancer easier for the immune system to detect and destroy

A new technology has been developed to increase the visibility of cancer cells to the immune system using CRISPR and could lead to a new way to treat cancer.

Major histocompatibility complex (MHC) class I molecules are an immune complex present on the surface of all cells in humans. MHC class I molecules are a prerequisite for the immune system to recognize and eliminate cancer. When cancer cells face pressure from the immune system, they actively reduce their MHC class I molecules, so the cancer cells can hide from attracting the attention of CD8⁺ T cells, the main cells of the immune system that fight cancer.

Researchers in Japan and the United States, led by Professor Koichi Kobayashi of Hokkaido University and Texas A&M Health Center, and Dr. Paul de Figueiredo, Bond LSC Principal Investigator and NEXTGEN Precision Health Professor at the University of Missouri, have developed technology to stably increases the amount of MHC class I in cancer cells. This development, a new method of enhancing the immune system’s ability to detect and eliminate cancer cells, is published in the journal Proceedings of the National Academy of Sciences.

“Our discovery has the potential to change the way we approach cancer treatment,” says Kobayashi. “Our technology allows us to specifically target immunosensitive genes and activate the immune system against cancer cells, offering hope to those resistant to current immunotherapy.”

Kobayashi and his team previously identified a gene called NLRC5 that regulates levels of MHC class I. They also discovered that NLRC5 is suppressed by turning off molecular switches that exist in the DNA in cancer—through a process called DNA methylation—to reduce of MHC class I levels.

Their technology, known as the TRED-I (targeted reactivation and demethylation for MHC-I) system, was able to restore DNA methylation of the NLRC5 gene and further activate NLRC5, thereby increasing MHC class I levels in cancer without causing serious side effects.

“New ways to fight cancer like this are desperately needed because we have few solutions to fight certain types of cancer,” de Figueiredo said. “It’s a radically new approach and I felt happy to be a part of it.”

TRED-I was tested in animal models of cancer. It significantly reduced tumor size and increased cytotoxic CD8 activity⁺ T cells. When used in conjunction with existing immunotherapy, TRED-I significantly increases treatment efficacy.

Unexpectedly, the TRED-I system was effective for the tumor located far from the original target tumor, showing potential for the treatment of metastatic cancer.

“This work is the culmination of our team’s research over the past decade,” concludes Kobayashi. “It’s great to shine a light on moving our discoveries to potential clinical applications.” We believe that with further refinement, the TRED-I system can make a significant contribution to cancer therapy.”

Further research will focus on the feasibility of directly delivering the TRED-I system to cancer patients. Such drugs could improve the efficiency of the immune system in eliminating cancer and could also improve the response to existing therapy.