Illustrated cross section of a lipid nanoparticle. The nanoparticles in this study contained a payload of adjuvants and cancer antigens. Credit: Love Employee/Getty Images
A nanoparticle system for delivering vaccines has been shown to prevent the development and reduce the spread of melanoma, pancreatic and triple-negative breast cancer in mice.
The team from the University of Massachusetts Amherst in the US believes their vaccine may also work preventively, with the hopes of one day applying their approach across multiple cancer types to help individuals at high risk for cancer.
“By engineering these nanoparticles to activate the immune system via multi-pathway activation that combines with cancer-specific antigens, we can prevent tumour growth with remarkable survival rates,” says Prabhani Atukorale, an assistant professor of biomedical engineering.
Antigens and adjuvants are the 2 main elements used to create vaccines.
The antigen is the piece of the disease-causing pathogen which the immune system is trained to recognise and eliminate. Adjuvants increase the immune response to the antigen.
“In recent years, we have come to understand how important the selection of the adjuvant is because it drives the second signal that is needed for the correct priming of T and B [immune] cells,” says Atukorale.
The team used a lipid nanoparticle developed in Atukorale’s previous research to encase the adjuvants and melanoma peptide antigens and gave this vaccine combination to mice.
Three weeks later, the mice were exposed to melanoma cells.
They found that 80% of the nanoparticle vaccinated mice remained tumour-free until the end of the study (250 days). All unvaccinated mice, or those vaccinated with non-nanoparticle formulation, developed tumours and none survived for more than 35 days.
The researchers found that their nanoparticle formulation switched on immune cells called T cells which were then primed to recognise and attack the melanoma peptide.
For the second experiment, the team combined the nanoparticles with a new antigen –tumour lysate, or killed cancer cells from a tumour mass. After 3 weeks, the mice were then exposed to either melanoma, triple-negative breast cancer or pancreatic ductal adenocarcinoma cells.
The researchers found that 88% of mice exposed to pancreatic cancer, 75% of those exposed to breast cancer and 69% of those exposed to melanoma rejected the tumour.
“The tumour-specific T-cell responses that we are able to generate – that is really the key behind the survival benefit,” says first author of the paper, Griffin Kane, also a researcher at UMass Amherst.
“There is really intense immune activation when you treat innate immune cells with this formulation, which triggers these cells to present antigens and prime tumour-killing T cells.”
These results have been published in Cell Reports Medicine.
Metastatic cancer cells spread from their original location to different parts of the body. Previous studies have found that approximately 80% of patients living with metastatic cancer will die of their diagnosed cancer.
“The vast majority of tumour mortality is still due to metastases, and it almost trumps us working in difficult-to-reach cancers, such as melanoma and pancreatic cancer,” says Atukorale.
“Metastases across the board is the highest hurdle for cancer.”
When mice from the first experiment were exposed to melanoma cells systemically, which mimics how cancer metastasises, only those that received the nanoparticle vaccine did not develop lung tumours.
“That is a real advantage of immunotherapy, because memory is not only sustained locally,” says Atukorale.
“We have memory systemically, which is very important. The immune system spans the entire geography of the body.”
The team is now focusing on developing their adjuvant into a therapeutic vaccine that is safe for humans.