The incidence of fungal infections, especially those caused by Aspergilllus, has been on the rise in cancer patients. Treatments to combat cancer results in reduced immunity in patients, making them more susceptible to infections. The efficacy of antifungal agents has diminished over the decades, making it necessary to find new ways to combat these potentially fatal pathogens.
To address this growing need, researchers at The University of Texas MD Anderson Cancer Center, led by Laurence Cooper, M.D., Ph.D, redirected immune cells to detect the presence of fungi, and prevent infections in cancer patients. The Sleeping Beauty gene transfer system was designed by the University of Minnesota, and is a method to stably introduce a gene of choice into human cells. Previously used methods of gene therapy involved the use of viruses. One of the risks with those approaches, however, was the chance of an immune reaction to the associated viral proteins and a reduction in efficacy of treatment. The Sleeping Beauty system bypasses this risk by using a transposon; a genetic element that allows the expression of a specific gene, that is not found in vertebrate genomes, and has very low chances of causing an immune reaction in patients.
This technology has been used in clinical trials at The University of Texas MD Anderson Cancer Center to detect molecules present on cancerous cells and destroy them. T-lymphocytes or T-cells are members of the immune system that are primarily involved in defending the body. In this study, clinical grade T-cells were engineered to express a chimeric antigen receptor (CAR) that allows these cells to recognize specific sugar molecules found on the surface of fungal cells. These repurposed immune cells were shown to recognize, damage and prevent the growth of Aspergillus fungal cells as per the expectations of the authors. Cooper is hopeful that these CAR-expressing T-cells can be used for targeting a broader range of pathogens and malignancies and will usher in a new mode of immunotherapy.
This study was published in the Proceedings of the National Academy of Sciences (PNAS) and co-authored by Dimitrios Kontoyiannis, M.D., professor in the Department of Infectious Diseases, and Richard Champlin, M.D., Ph.D., chair of the Department of Stem Cell Transplantation.