Cancers are notorious for secreting chemicals that confuse the immune system and thwarting biological defenses.
To counter that effect, some cancer treatments try to neutralize the cancer's chemical arsenal and boost a patient's immune response--though attempts to do both at the same time are rarely successful.
Now, researchers have developed a novel system to simultaneously deliver a sustained dose of both an immune-system booster and a chemical to counter the cancer's secretions, resulting in a powerful therapy that, in mice, delayed tumor growth, sent tumors into remission and dramatically increased survival rates.
The researchers, all from Yale University, report their findings in the July 15, 2012, issue of Nature Materials.
The new immunotherapy incorporates well-studied drugs, but delivers them using nanolipogels (NLGs), a new drug transport technology the researchers designed. The NLGs are nanoscale, hollow, biodegradable spheres, each one capable of accommodating large quantities of chemically diverse molecules.
The spheres appear to accumulate in the leaky vasculature, or blood vessels, of tumors, releasing their cargo in a controlled, sustained fashion as the spherule walls and scaffolding break down in the bloodstream.
For the recent experiments, the NLGs contained two components: an inhibitor drug that counters a particularly potent cancer defense called transforming growth factor-β (TGF-β), and interleukin-2 (IL-2), a protein that rallies immune systems to respond to localized threats.
"You can think of the tumor and its microenvironment as a castle and a moat," says Tarek Fahmy, the Yale University engineering professor and NSF CAREER grantee who led the research. "The 'castles' are cancerous tumors, which have evolved a highly intelligent structure--the tumor cells and vasculature. The 'moat' is the cancer's defense system, which includes TGF-β. Our strategy is to 'dry-up' that moat by neutralizing the TGF-β. We do that using the inhibitor that is released from the nanolipogels. The inhibitor effectively stops the tumor's ability to stunt an immune response."
At the same time, the researchers boost the immune response in the region surrounding the tumor by delivering IL-2--a cytokine, which is a protein that tells protective cells that there is a problem--in the same drug delivery vehicle. "The cytokine can be thought of as a way to get reinforcements to cross the dry moat into the castle and signal for more forces to come in," adds Fahmy. In this case, the reinforcements are T-cells, the body's anti-invader 'army.' By accomplishing both treatment goals at once, the body has a greater chance to defeat the cancer.
