A new study exploring how pasteurization, an increasingly common technique for streamlining production of medical end products, can minimize toxicity and improve the efficacy of immunotherapy for some solid tumors has identified an important driving factor that sets Pasteur’s™ apart from other technologies.
The research, led by researchers from the Translational Cancer Research Institute (TCRI) at UCLA and a large clinical trial registry, found that when Pasteur extracts were exposed to heat to break down the protein-encoding catalytic cycle in a cancer cell, it improved the ability the tumor tissue to fight off, a hallmark of solid tumors.
In their study, published in Cell Reports, the researchers compared the ability of hadithioma, a small type of solid tumor, to control tumors on varying degrees of immunotherapy (T-cells), and to surgate basal-like and medulloblastoma, two brain cancers with varying degrees of immunotherapy. A control group of financial backers did not receive T-cell exposure.
The research team found that as pasteurization increased, it degraded the tumor-fighting capacity of hadithioma and normalized its T-cell effector response. The two cancers were genetically identical except for the tumor marker for pheochromocytoma — the most common type of brain tumor in men.
These findings demonstrate the impact of Pasteur’s™ technology not only for solid tumors but also for multiple types of brain cancer because it enhances the protective effect of immunotherapy.”
Jun Young Kim, PhD, assistant professor of physiology at the David Geffen School of Medicine at UCLA and one of the principal investigators of the study.
Cellular proteins in tumors are made up of their own protein catalytic cycle, called cytochrome P450 2 (Py2+) and its interaction with enzymes known as enzymes of glycosylation, which are ubiquitous in many cancers. Mutations in Py2+ or P450 enzymes are associated with many cancer types but is not common in normal tissues.
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In the study, Kim and his colleagues used a mouse model where mice do not express or express the enzyme knownoglycosylation which does occur in the majority of human and animal specimens. They expressed tumor-associated Fas in tumor tissue of the mice that did not express the enzyme, and in a mouse model where human cancer cells exposed to doses of chemotherapy diminished the amount of Fas1 and Fas2 in their tumor tissues. This allowed them to accurately detect the effects of improving the ability of a tumor given immunotherapy to respond to immunotherapy, and also of using the immunotherapy in combination with other immunotherapy. Their results were mirrored in a mouse model where Fas1 and Fas2 levels did not be stably maintained. Once they understood the significance of their findings, they identified a new molecule gene that encodes a protease that can be used to boost tumor responses to cancer immunotherapies.