Researchers have developed a way of 'backpacking' immunotherapeutic drugs so as to boost their effectiveness and minimize the side effects.
Immunotherapy enhances people's immune cells in order to boost the body's natural defenses against cancer.
Two prominent ways of doing this are:
- removing tumor-specific T cells — which are specialized immune cells — from a person's own tumor, and then growing them in the laboratory before re-administering them to the patient intravenously
- isolating already circulating T cells in a patient's blood and then "training" them to target tumor-specific proteins — either by genetically modifying them, or by exposing them to such proteins, so that they can adapt
But while these strategies have shown promise in the treatment of blood cancers, such as leukemiaor lymphoma, they do not seem to be as effective in the treatment of solid tumors, such as those seen in breast cancer, for instance.
A team from the Massachusetts Institute of Technology (MIT) in Cambridge is now developing a way to boost the effect of T cells against solid tumors while avoiding side effects.
The scientists are testing the use of specialized nanoparticles carrying immune-boosting drugs capable of attaching to T cells.
"We found you could greatly improve the efficacy of the T cell therapy with backpacked drugs that help the donor T cells survive and function more effectively. Even more importantly, we achieved that without any of the toxicity that you see with systemic injection of the drugs."
Senior study author Prof. Darrell Irvine
The researchers' paper is now published in the journal Nature Biotechnology.
More effective drug delivery
In order to enhance the effect of T cells against solid cancer tumors, researchers have previously tried injecting larger quantities of cytokines, which are immune response-stimulating substances.
However, cytokines can have damaging effects, since they are hard to control and might amplify the activity of specialized cells that do not require this boost.
Therefore, the MIT researchers decided to try to circumvent this obstacle by creating a "receptacle" to contain the immune-boosting drug that was capable of attaching only to certain types of T cells and stimulating them without affecting the activity of other cells.
So, they created a type of nanoparticle able to carry enough of the cytokines to allow the T cells to do their best work, and which would only release the substances once the immune cells they are attached to actually reach a cancer tumor.
The nanoparticles are made out of a specialized gel, the molecules of which are held together by bonds designed to dissolve when the T cells experience a slight chemical shift as a result of their interaction with tumor cells.
"That allowed us to link T cell activation to the drug release rate," says Prof. Irvine. "The nanogels are preferentially dissolving when the T cells are in sites where they see tumor antigen: in the tumor and in the tumor-draining lymph nodes."
"The drug is most efficiently being released," he adds, "at the sites where you want it and not in some healthy tissue where it might cause trouble."
Clinical trials on the horizon?
The researchers assessed the effectiveness of their new strategy in mice whose T cells had been genetically modified to target a protein specific to melanoma (or skin cancer).
Happily, the researchers saw that their experimental immunotherapy approach destroyed the cancer tumors in approximately 60 percent of the rodents after multiple exposure to this treatment.
They also discovered that delivering the drug using the specially designed nanoparticles resulted in no harmful side effects. This is in stark contrast to some of the negative outcomes observed when the same quantity of the immune-boosting drug was injected into the bloodstream.
Moreover, when testing this method on human T cells engineered to target glioblastoma (or brain cancer) tumors, the team observed that, once again, it showed promising results.
As one of the co-founders of Torque Therapeutics — who are a company researching and testing novel immunotherapy methods for the treatment of cancer — Prof. Irvine aims to start conducting clinical trials for this new approach this very summer.
He and his team hypothesize that "backpacking" the immune-stimulating drug may be effective in treating any solid tumors or blood cancers, and they aim to test its effect in more types of cancer.
They also plan on investigating whether other types of drug than the one used in their recent experiments could be even more effective in boosting T cell activity.