Targeting the Immune System to Attack Cancer
2/12/2008


Even as the human immune system protects the body by identifying bacteria, viruses, and other foreign invaders and then destroying them, it often allows dangerous cancerous tumors to grow unchecked. Australian researchers have discovered that by injecting substances that mimic viral infections into tumors, they can help the immune system better target those tumors for destruction.

Foreign organisms such as bacteria and viruses contain proteins called antigens, which stimulate an immune system response. Specialized immune cells known as killer T cells recognize these antigens, bind to the infected cells, and destroy them.

Though the immune system also can theoretically recognize tumor antigens, tumors have developed a variety of ways to protect themselves. For example, they might block or destroy killer T cells before they can attack, select tumor cells that are missing antigens, or use a combination of evasive tactics to interfere with antigen presentation and block the immune response.

“There appears to be multiple layers of suppression used by any given tumor,” explains author Andrew Currie, PhD, Senior Research Fellow at the School of Medicine & Pharmacology, QEII Medical Centre in Western Australia. “Not only that; the tumors are not passive suppressors, but rather astute manipulators of the immune system. As one suppressive pathway is overcome, others pop up – this is probably why immune therapies have been so disappointing to date.” Immune therapies currently in use include interleukin-2, interferon, and cancer vaccines, which are designed to help the body’s immune system attack cancer cells.

In their research, lead authors Dr. Currie and Dr. Robbert van der Most, PhD, chose a different approach, injecting substances called toll-like receptor (TLR) agonists into tumors. These TLRs mimic the response that would occur if a viral infection were present, alerting the immune system that there are foreign substances in the area. “Activation of these receptors provides the immune system with context, namely that of danger,” explains Dr. Currie. When the TLRs are warning of danger and the tumor antigens are within the same environment, the immune system is primed to also see the tumor antigens as dangerous.

When the researchers injected TLR agonists into mouse mesothelioma cells, tumors completely went away in 40 percent of the mice. All of the remaining mice showed at least some slowing of cancer progression. However, the therapy was only effective when killer T cells were already present, says Dr. Currie.

It’s far too early to definitively halt cancer growth by this method, especially since mouse models don’t always translate into human treatment successes and tumors can be difficult to target when they’re spread throughout the body. However, Dr. Currie believes that this therapy might be promising not only for treating mesothelioma, but also for other cancers in the future. "Mesothelioma" is a very difficult tumor to treat, so if a therapy can succeed in this tumor, I think it bodes well for responses in more responsive tumor types,” he says.


Source:

Currie AJ, et al. Targeting the effector site with IFN- áâ-inducing TLR ligands reactivates tumor-resistant CD8 T cell responses to eradicate established solid tumors. The Journal of Immunology, 2008;180:1535-1544.



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