Yale University researchers have come up with a new method that not only delivers a sustained dose of immune system booster, but also releases a chemical to counter cancer's secretions.
This resulted in a powerful therapy that delayed tumour growth, sent tumours into remission and dramatically increased survival rates in mice.
AdvertisementCancers are notorious for secreting chemicals that confuse the immune system and thwarting biological defences.
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.
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 tumours, 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-B (TGF-B), and interleukin-2 (IL-2), a protein that rallies immune systems to respond to localized threats.
"You can think of the tumour and its microenvironment as a castle and a moat," Tarek Fahmy, the study leader from Yale University, said.
"The 'castles' are cancerous tumours, which have evolved a highly intelligent structure-the tumour cells and vasculature. The 'moat' is the cancer's defense system, which includes TGF-B.
"Our strategy is to 'dry-up' that moat by neutralizing the TGF-B. We do that using the inhibitor that is released from the nanolipogels. The inhibitor effectively stops the tumour's ability to stunt an immune response," Fahmy said.
At the same time, the researchers boost the immune response in the region surrounding the tumour 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," Fahmy said.
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.
The current study targeted both primary melanomas and melanomas that have spread to the lung, demonstrating promising results with a cancer that is well-suited to immunotherapy and for which radiation, chemotherapy and surgery tend to prove unsuccessful, particularly when metastatic.
The researchers did not evaluate primary lung cancers in this study.
The study has been published in Nature Materials.