@MIT: Synergy needed to Supress Cancer Tumors: Activation of the Innate Immune System AND Stimulation of T cells – the adaptive immune system
Reporter: Aviva Lev-Ari, PhD, RN
Press Release
Immune synergy
To their surprise, the researchers found that T cells were the most important component of the anti-tumor response induced by the antibody-IL-2 combination. They believe that the synergy of IL-2-induced cells and cytokines, and the antibody treatment, creates an environment that lets T cells attack more effectively.
“The antibody-driven innate response creates an environment such that when the T cells come in, they can kill the tumor. In its absence, the tumor cells establish an environment where the T cells don’t work very well,” Wittrup says.
Cells called neutrophils, which are considered the immune system’s “first line of defense” because they react strongly to foreign invaders that enter the skin through a cut or other injury, were also surprisingly important.
“They’re a really powerful force in your immune system, but people in immunotherapy don’t usually focus on neutrophils. They don’t really consider them as a viable tool,” Zhu says. “It pointed us to the idea that although T cells and natural killer cells are important, maybe we’re forgetting about a part of the immune system that is also really important and could help us achieve our goals of ultimately curing the tumors.”
The researchers also found that when they delivered an antibody, IL-2, and T cells targeted to the tumor, the adoptively transferred T cells killed cancer cells much more successfully than when only T cells were delivered. In 80 to 90 percent of the mice, tumors disappeared completely; even when tumor cells were reinjected into the mice months after the original treatment, their immune systems destroyed the cells, preventing new tumors from forming
In a related paper that appeared recently in the Proceedings of the National Academy of Science, the MIT team also found that delivering IL-2 bound to any kind of antibody, even if the antibody did not target a protein on the tumor cell surface, would halt or slow tumor growth, especially if additional doses of the antibody alone were also given. Graduate student Alice Tzeng was the lead author of that study.
The researchers are now exploring additional proteins that could be added to the IL-2 and antibody combination to make immunotherapy more effective. In the meantime, simply giving patients more prolonged exposure to IL-2 could improve the effectiveness of existing antibody drugs, Wittrup says.
The research was funded by the National Cancer Institute, the National Institute for General Medical Sciences, and the National Science Foundation.
SOURCE
Leave a Reply