Researchers at the University of Texas Southwestern Medical Center have identified a genetic mutation that slows the growth of melanoma and potentially other types of cancer by mobilizing the immune system. The findings were published in the Journal of Experimental Medicine.
Dr. Huxin Shu, a lecturer at the Center for Genetics and Immunology, stated that the results indicate the possibility of using a completely new type of therapeutic target to combat a wide range of malignant tumors. He co-authored the study with Bruce Beutler, director of the Center for Genetics and Immunology, a professor of immunology and internal medicine, and a Nobel laureate in Physiology or Medicine in 2011.
The scientists identified several genes known as oncogenes that promote and direct cancer cells when mutated. Although researchers have long claimed that there are mutations in the human genome that protect against cancer, their detection has been challenging since individuals with these genetic mutations do not differ significantly from others.
In their search for such genes, Dr. Shu and Dr. Beutler, along with their colleagues, created mouse models with various genetic mutations and searched for mice that did not develop malignant tumors. They applied a method developed in Beutler's laboratory called Automated Meiotic Mapping (AMM), which tracks abnormal features in mice with genetic mutations.
The researchers quickly identified the gene H2-Aa. Mice carrying two mutations of this gene, which result in the complete absence of the H2-Aa protein, often do not develop tumors after exposure to melanoma cells. In contrast, mice with only one mutation of this gene showed significantly limited tumor development compared to those carrying the wild-type form of the gene. H2-Aa is associated with the production of part of the MHC class II protein, which helps the immune system distinguish between proteins, thereby preparing to attack potential external threats.
The study authors were also able to synthesize a monoclonal antibody protein that blocks the action of other proteins against H2-Aa, leading to the same outcome as H2-Aa mutations.