Convincing the Immune System To Attack Cancer Cells

Cancer researchers have used a two-pronged approach to stimulate the immune system to recognize cancer cells and destroy tumors.

Since cancer cells are normal cells, which lost the molecular control mechanisms that prevent unregulated growth and proliferation, the immune system does recognize them as "invaders” but does not act to destroy them. A possible approach to cancer therapy is to fool the immune system into rejecting tumor cells.

Towards this end, investigators at the Scripps Research Institute (La Jolla, CA, USA) decided to manipulate both the innate and adaptive immune systems. In order to boost the activity of killer T cells they used a complex comprising interleukin-2 (IL-2) and IL-2 antibodies. This type of complex previously had been shown to activate T cells and produce a more robust T cell response. However, this response faded away if the IL-2/antibody complex was removed.

To generally fire up the immune system and maintain enhanced T cell response, they used poly(I:C), which targets the innate immune system. Poly(I:C) is a synthetic polymer of inosine that resembles the RNA of infectious viruses and is used to stimulate the production of interferon by the immune system.

Results published in the October 20, 2008, online edition of the journal the Proceedings of the [U.S.] National Academy of Sciences (PNAS) revealed that in a mouse model a combination of specific tumor antigen, the IL2/antibody complex, and poly(l:C) delivered all at the same time prevented tumor growth without being toxic to the animals. This strategy mimicked many of the benefits of whole-body irradiation, including the provision of high levels of homeostatic cytokines, enhanced expansion of effector cells relative to regulatory T cells, and provision of inflammatory cytokines.

"The problem with cancer is that it becomes part of what the immune system identifies as "self” and there are ways the body learns to tolerate "self” to prevent immune attack,” explained senior author Dr. Linda Sherman, professor of immunology at the Scripps Research Institute. "Hitting it with these new tools basically gets the immune system to pay attention to the cancer, and go after it.”

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