vaccine attenuator: Overcoming Tumor Supression

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Novel Way To Develop Tumor Vaccines: Regulate Immune Inhibitor To Overcome

Tumor Supression

ScienceDaily (Mar. 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.

" 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 system's

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.

http://www.sciencedaily.com/releases/2008/03/080302150718.htm