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USC researchers discover novel way to develop tumor vaccines
Date:3/2/2008

LOS ANGELES, March 2, 2008 Researchers at the University of Southern California (USC) have uncovered a new way to develop more effective tumor vaccines by turning off the suppression function of regulatory T cells. The results of the study, titled A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell-mediated suppression, will be published in Nature Medicine on March 2, 2008.

Under normal circumstances, regulatory T cells inhibit the immune system to attack its own cells and tissues to prevent autoimmune diseases. Cancer cells take advantage of regulatory T cells' suppressor ability, recruiting them to keep the immune system at bay or disabling the immune systems attack provoked by tumor vaccines. says Si-Yi Chen, M.D., Ph.D., professor of immunology and molecular microbiology at the USC/Norris Comprehensive Cancer Center and the Keck School of Medicine of USC. Our study provides a new vaccination strategy to overcome the regulatory T cells immune suppression while avoiding non-specific overactivation of autoreactive T cells and pathological autoimmune toxicities.

The study identified a new molecular player called A20, an enzyme that restricts inflammatory signal transduction in dendritic cells. When it is inhibited, the dendritic cells overproduce an array of cytokines and co-stimulatory molecules that triggers unusually strong immune responses that cannot be suppressed by regulatory T cells. The resulting hyperactivated immune responses triggered by A20-deficient dendritic cells are capable of destroying various types of tumors that are resistant to current tumor vaccines in mice.

Through a series of immunological studies, we have identified A20 as an essential antigen presentation attenuator that prevents the overactivation and excessive inflammation of the dendritic cells, which, in turn, restricts the potency of tumor vaccines, says Chen.

The immune systems dendritic cells are the gua
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Contact: Jennifer Chan
chanj@usc.edu
323-442-2830
University of Southern California
Source:Eurekalert

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