by A groundbreaking technology has been developed to increase the visibility of cancer cells to the immune system, potentially revolutionizing cancer treatment. This new approach utilizes CRISPR gene editing to augment the presence of major histocompatibility complex (MHC) class I molecules on the surface of cancer cells.
MHC class I molecules are essential for the immune system to recognize and eliminate cancer cells. However, these cells actively reduce their MHC class I molecules when faced with immune system pressure, enabling them to evade detection by CD8+ T cells, which are the primary cancer-fighting cells in the immune system.
A team of researchers from Japan and the United States, led by Professor Koichi Kobayashi of Hokkaido University and Dr. Paul de Figueiredo of the University of Missouri, has developed a novel technology to significantly increase the levels of MHC class I in cancer cells. Their findings, published in the journal Proceedings of the National Academy of Sciences, offer a promising approach to enhance the immune system’s ability to identify and destroy cancer cells.
Professor Kobayashi explains the potential impact of this discovery, stating, “Our technology enables us to specifically target immune responsive genes and activate the immune system against cancer cells, offering hope to those who are resistant to current immunotherapy.”
The researchers previously identified a gene called NLRC5 that controls the levels of MHC class I. They also discovered that NLRC5 is suppressed in cancer cells through a process called DNA methylation, reducing the levels of MHC class I. The team’s new technology, known as the Targeted Reactivation and Demethylation for MHC-I (TRED-I) system, restores the DNA methylation of the NLRC5 gene and activates NLRC5, leading to increased MHC class I levels in cancer cells without severe side effects.
To evaluate the efficacy of the TRED-I system, the researchers conducted tests using animal cancer models. They observed a significant reduction in tumor sizes and increased activity of cytotoxic CD8+ T cells, which are responsible for directly killing cancer cells. When combined with existing immunotherapy, the TRED-I system demonstrated enhanced treatment effectiveness.
Furthermore, the TRED-I system unexpectedly exhibited efficacy against tumors located distantly from the original targeted tumor, suggesting its potential for treating metastasized cancers.
Professor de Figueiredo, one of the principal investigators, emphasizes the importance of this innovation in cancer treatment, stating, “New modalities for fighting cancer like this are desperately needed because we have few solutions to fight some cancer types. This is a radically new approach, and I’ve felt lucky to be part of it.”
The next phase of the research will focus on enabling the direct delivery of the TRED-I system to cancer patients. The development of drugs based on this technology could greatly improve the immune system’s ability to eliminate cancer cells and enhance the response to existing therapies.
“This work is the culmination of our team’s research over the past decade,” concludes Professor Kobayashi. “With further refinement, we believe the TRED-I system could significantly contribute to cancer therapy and pave the way for potential clinical applications.”
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
