Researchers have shown that a nanoparticle-based vaccine can prevent several aggressive types of cancer in mice, providing long-lasting immune protection and blocking metastasis.
The treatment activated a powerful immune memory, keeping up to 88 percent of vaccinated mice tumor-free and stopping the spread of cancer. By teaching the immune system to target cancer antigens, the vaccine has shown long-lasting protection and broad potential.
Potent cancer prevention in mice
A research team at the University of Massachusetts Amherst has demonstrated that a nanoparticle-based vaccine can successfully prevent melanoma, pancreatic cancer and triple-negative breast cancer in mice. Depending on the type of cancer, up to 88 percent of vaccinated mice remained tumor-free (depending on the type of cancer), and the approach reduced — and in some cases completely blocked — the spread of cancer in the body, writes SciTechDaily.
“By designing these nanoparticles to activate the immune system through multi-pathway activation that combines with cancer-specific antigens, we can prevent tumor growth with remarkable survival rates,” says Prabhani Atukorale, assistant professor of biomedical engineering in the Riccio College of Engineering at UMass Amherst and corresponding author of the paper.
Atukorale’s previous studies found that his nanoparticle-based drug could shrink or eliminate existing tumors in mice. The new results show that the same technology also works as a preventive strategy.
Melanoma antigen vaccine testing
In the first phase of the study, the researchers paired the nanoparticle platform with well-known melanoma peptides (called an antigen, similar to how a flu vaccine typically contains parts of the inactivated flu virus). This combination activated the T cells, which were then primed to recognize and destroy the melanoma cells. Three weeks after vaccination, the mice were exposed to melanoma.
Eighty percent of the mice given this “super adjuvanted” nanoparticle vaccine remained tumor-free and survived the entire 250-day study. Every mouse that received a traditional vaccine, a formulation without nanoparticles, or no vaccine developed tumors, and none survived more than 35 days.
The vaccine also prevented melanoma from spreading to the lungs. When the mice were systemically exposed to melanoma cells in a manner that mimics metastasis, none of the nanoparticle-vaccinated mice formed lung tumors, while all other mice did.
“Metastases in general represent the biggest obstacle to cancer” says Atukorale. “The vast majority of tumor mortality is still due to metastases and almost overtakes us working in hard-to-reach cancers such as melanoma and pancreatic cancer.“
Long-lasting immune memory throughout the body
Atukorale refers to this protection as “immune memory“. “This is a real advantage of immunotherapy because the memory is not only supported locally”she says. “We have system memory, which is very important. The immune system spans the entire geographic surface of the body.”
The first round of testing used antigens designed specifically for melanoma. However, developing personalized antigens for each type of cancer often requires whole genome sequencing or advanced bioinformatics. To address this challenge, the researchers conducted a second experiment using destroyed cancer cells from the tumor itself, known as tumor lysate. Mice vaccinated with this nanoparticle lysate formulation were then challenged with melanoma, pancreatic ductal adenocarcinoma, or triple-negative breast cancer cells.
High rates of tumor rejection in several types of cancer
The results were amazing. Tumor rejection was observed in 88% of pancreatic cancer cases, 75% of breast cancer cases and 69% of melanoma cases. Each vaccinated mouse that remained tumor-free also resisted metastases when subsequently exposed systemically to cancer cells.
“The tumor-specific T-cell responses that we’re able to generate – that’s actually the key to the survival benefit”says Griffin Kane, a postdoctoral research associate at UMass Amherst and first author of the paper. “There’s a really intense immune activation when you treat innate immune cells with this formula, which triggers those cells to present antigens and stimulate tumor-killing T cells.”
How Nanoparticle Vaccine Creates Strong Immune Response
This powerful T-cell activation is possible due to the unique structure of the nanoparticles used in the vaccine.
Vaccines – regardless of the target disease – include two main components: the antigen and the adjuvant. The antigen is the part of the pathogen (in this study, cancer cells) that tells the immune system what to attack. The adjuvant stimulates the immune system so that it recognizes the antigen as a threat and triggers a strong response.
Atukorale’s lab designs its vaccines to mimic the way pathogens naturally alert the immune system. Effective immune activation requires multiple signals of “danger” which act through different pathways. “In recent years, we have come to understand how important adjuvant selection is because it triggers the second signal required for proper priming of T and B cells”, says Atukorale.
Many promising adjuvants used in cancer immunotherapy do not mix well at the molecular level, similar to the way oil and water separate. To address this limitation, the team created a lipid nanoparticle “superadjuvant” that can encapsulate and deliver two different immune-boosting ingredients in a stable and coordinated manner.
Towards a Broad Cancer Vaccination Platform
The researchers believe that this nanoparticle system provides a flexible platform that could be tailored to many types of cancer.
They also see potential for both treatment and prevention, especially for people who face a high risk of developing cancer. This concept became the foundation of a startup launched by Atukorale and Kane called NanoVax Therapeutics.
“The core technology on which our company was founded is this nanoparticle and this therapeutic approach”says Kane. “This is a platform developed by Prabhani. The startup allows us to pursue these translational efforts with the ultimate goal of a improve patients’ lives.”
