For the first time, researchers have shown that using a nanovaccine to deliver cancer immunotherapy can slow tumor growth and prolong survival in mouse models of several types of cancer.
The team – from the University of Texas Southwestern (UTSW) Medical Center in Dallas – describes the work in the journal Nature Nanotechnology.
Immunotherapy is a way of treating disease by getting the body’s immune system to fight it.
When that disease is cancer, it is “critically important” that the immunotherapy generates immune cells called T cells that can recognize and target tumor cells for elimination.
One way to do this is to apply the principle of a vaccine, where antigens – molecules that uniquely identify the target – are delivered to the immune system to prime it to recognize and destroy the disease-causing cells.
Co-senior author Jinming Gao, a UTSW professor of pharmacology and otolaryngology, says that various established vaccine approaches – such as using live bacteria as the delivery mechanism – have been used in cancer immunotherapy.
However, he notes that these tend to be complex and costly, and they can also result in immune-related side effects.
The approach that the UTSW researchers have developed – which they describe as a “minimalist nanovaccine” – comprises a simple mixture of a tumor antigen and a synthetic polymer nanoparticle.
Nanoparticles are being increasingly used in medicine as they allow scientists to manipulate materials at the level of individual atoms, which is a very useful scale for tackling disease inside cells.
A significant advantage of UTSW’s nanovaccine approach is that the nanoparticles take the antigen directly to the lymph nodes to help generate primed T cells.
Prof. Gao says that conventional vaccines do not do this – they require the immune cells to collect the antigens in a “depot system” first and then transport them to the lymph nodes to prime the T cells.
For the vaccine to work, it has to first deliver the antigens into a type of immune cell called an antigen-presenting cell. The antigen-presenting cells process and present the antigens for recognition by the T cells.
The process of priming the immune response is not simply a case of delivering the antigen. At the same time, there has to be a signal that also triggers the immune response to use the antigen.
The researchers note that their experimental nanovaccine does this by triggering an adaptor protein called STING.
Co-senior author Zhijian J. Chen, professor of molecular biology at UTSW, sums up how their nanovaccine performs all the necessary steps:
“For nanoparticle vaccines to work, they must deliver antigens to proper cellular compartments within specialized immune cells called antigen-presenting cells and stimulate innate immunity. Our nanovaccine did all of those things.”
The team tested the nanovaccine on a variety of mouse models of cancer, including colorectal cancer, melanoma, and HPV-associated head, neck, cervix, and anogenital cancers. They note that in nearly all cases, the treatment led to slower tumor growth and prolonged survival.
The researchers are now teaming up with UTSW doctors to look at how to use the new nanovaccine in the clinic for a variety of cancers.
They believe that it is also possible to increase the anti-tumor effectiveness of the treatment by combining it with other immunotherapies, radiotherapy, and checkpoint inhibitors.
“What is unique about our design is the simplicity of the single-polymer composition that can precisely deliver tumor antigens to immune cells while stimulating innate immunity. These actions result in safe and robust production of tumor-specific T cells that kill cancer cells.”
Prof. Jinming Gao