Immunotherapy: Focus Area Three

By past MPN Research Foundation grantee (MF Challenge) Pearlie K. Burnette PhD, PharmD, Moffitt  Cancer Center

The immune system is made up of many types of cells and secreted factors that act together to defend against infections and remove damaged tissues. In the case of cancer, normal cells and cancer cells appear different, and thus, alarm the immune system to activate an attack. It is apparent that mutant cells giving rise to cancer must learn how to avoid detection by the immune system in order to expand in the body. Sometimes the cancer cells even harness immune factors for their own benefit.

The MPN Research Foundation has recently funded two exceptional scientific projects focused on immune function in MPNs. One project will be conducted at the University of California, Irvine, CA under the direction of Angela G. Fleischman, MD, PhD and the other project will be headed by Robert Kralovics, PhD from the Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna, Austria.

Three different genes can be causative in MPNs when mutated. Dr Fleischman found that mice lacking certain immune cells, T-lymphocytes and B-lymphocytes, fail to develop MPN despite having “cancer” cells that carry the mutant gene. They identified one specific factor produced by lymphocytes called Tumor Necrosis Factor-alpha (TNFα) that may be important in aiding in the progression or expansion of the mutant cells. Dr. Fleischman’s group will use an animal model to confirm the role of TNF-α in disease progression in MPN. They believe that a better understanding of this process will reveal new ways to delay or prevent the disease by blocking the immune factors hijacked by the mutant cells.

Dr. Kralovics is proposing to develop a new type of immunotherapy called a “cancer vaccine”.  According to the National Cancer Institute, immunotherapy is defined as “a treatment that boosts or restores the ability of the immune system to fight cancer”.  This group will focus on the mutant calreticulin (CALR) gene that is newly identified as a cause of MPN in many patients. They believe that the immune system can be triggered to recognize mutant calreticulin while sparing normal calreticulin. The potential efficacy of the new vaccine will be tested in the lab using cell lines and in an animal model of MPN.  Collectively, modifying the immune system is a fast evolving new frontier in the war against cancer. Finding ways to harness this complex group of cells and factors may lead to revolutionary new forms of therapy in MPN.

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