HAYWARD, Calif., Aug. 14, 2020 (GLOBE NEWSWIRE) — A multi-site research team headed by Dr. Ruoning Wang at the Nationwide Children’s Hospital has uncovered a metabolic pathway that can potentially be exploited to enhance the killing of anti-cancer T cells such as CAR-T cells. Immunotherapies using T cells have been shown to be effective in clinical treatment against B cell leukemias and checkpoint blockade therapies in melanoma, non-small-cell lung cancer, bladder cancer, and others. However, the success of the T cell therapy is limited to less than one-quarter of cancers. Hence, many cancer researchers are looking for novel ways to improve T cell based cancer therapies.
The approach of the research team was to study the metabolic fitness of T cells. Cancer cells are metabolically strong, and solid tumors create a tumor microenvironment which presents challenges and barriers to block the normal immune response spearheaded by T cells. Essentially, the cancer cells too often outcompete the immune cells called effector T cells. Human effector T cells were prepared and tested using Biolog’s Phenotype MicroArray
Dr. Wang’s team further showed that the ability of the effector T cells to consume inosine required the enzyme purine nucleoside phosphorylase (PNP). This enzyme converts inosine to hypoxanthine plus ribose-1-phosphate, an important metabolite that can be utilized by cells for growth and energy production. Some cancer cells also have PNP and can therefore still compete for inosine with the effector T cells. However for those cancer types with little or no PNP, the effector T cells can outcompete the cancer cells and significantly extend the life of mice with implanted tumors. Experiments showed that provision of inosine enhances the killing of PNP deficient cancer cells both with CAR-T cells and with T cells provided antibodies against checkpoint blockade inhibitors such as PDL-1.About Biolog, Inc.Biolog is a privately held company based in Hayward, CA, that continues to lead in the development of powerful new cell analysis tools for solving critical problems in biological, pharmaceutical, and biotechnological research and development. It is the world leader in phenotypic cell profiling. In addition to the Phenotype MicroArray
Andrew Wung
(510) 670-3336
awung@biolog.com
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