Researchers at the University of Massachusetts Amherst have shown that their nanoparticle-based vaccine can successfully prevent several aggressive cancers in mice, including melanoma, pancreatic cancer, and triple-negative breast cancer. Depending on the cancer type, up to 88% of vaccinated mice stayed tumor-free (depending on the cancer), and the vaccine also reduced — and in some cases completely prevented — the spread of cancer throughout the body.
“By engineering these nanoparticles to activate the immune system via 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 on the paper.
Atukorale had previously shown that her nanoparticle-based drug design could shrink or eliminate tumors in mice. The new findings reveal that this approach can also prevent cancer from forming in the first place.
In the first experiment, her team combined the nanoparticle system with well-studied melanoma peptides (called an antigen, similar to how a flu shot typically contains parts of the inactivated flu virus). This formulation activated immune cells known as T cells, training them to detect and destroy melanoma cells. Three weeks later, the vaccinated mice were exposed to melanoma.
Eighty percent of the mice that received the “super adjuvant” nanoparticle vaccine remained tumor-free and survived the entire study period (250 days). In contrast, all of the mice that received traditional vaccines, non-nanoparticle formulations, or no vaccine at all developed tumors and died within 35 days.
The vaccine also stopped cancer from spreading to the lungs. When the mice were systemically exposed to melanoma cells to mimic metastasis, none of the nanoparticle-vaccinated mice developed lung tumors, while every other mouse did.
“Metastases across the board is the highest hurdle for cancer,” says Atukorale. “The vast majority of tumor mortality is still due to metastases, and it almost trumps us working in difficult-to-reach cancers, such as melanoma and pancreatic cancer.”
Atukorale refers to this protection as “memory immunity.” “That is a real advantage of immunotherapy, because memory is not only sustained locally,” she explains. “We have memory systemically, which is very important. The immune system spans the entire geography of the body.”
The first phase of testing used a vaccine with known antigens designed for melanoma. However, creating antigens for each cancer type can require extensive genome sequencing or bioinformatics analysis. To simplify the process, the researchers tested a second version using killed tumor cells, called tumor lysate, derived directly from the cancer itself. Mice vaccinated with this nanoparticle lysate vaccine were later exposed to melanoma, pancreatic ductal adenocarcinoma, or triple-negative breast cancer cells.
The results were impressive: 88% of mice with pancreatic cancer, 75% with breast cancer, and 69% with melanoma rejected tumor formation. Furthermore, all mice that remained tumor-free after vaccination also resisted metastasis when exposed systemically to cancer cells.
“The tumor-specific T-cell responses that we are able to generate — that is really the key behind the survival benefit,” says Griffin Kane, postdoctoral research associate at UMass Amherst and first author on the paper. “There is really intense immune activation when you treat innate immune cells with this formulation, which triggers these cells to present antigens and prime tumor-killing T cells.”
This robust T-cell response is possible because of the particular nanoparticle design of the vaccine.
Vaccines — regardless the target disease — contain two primary components: The antigen and the adjuvant. The antigen is the piece of the disease-causing pathogen (in this study, cancer cells) that the immune system can be trained to target. The adjuvant is a substance that activates the immune system to recognize the antigen, treat it as a foreign intruder and eliminate it.
The Atukorale Lab draws inspiration from how pathogens naturally stimulate the immune system. To mount a strong immune response, the body requires multiple “danger” signals triggered through different pathways. “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 cells,” says Atukorale.
However, just like oil and water, many of the most promising adjuvants for cancer immunotherapy do not mix well at the molecular level. To overcome this, the Atukorale Lab has engineered a lipid nanoparticle-based “super adjuvant” capable of stably encapsulating and co-delivering two distinct immune adjuvants that activate immunity in a coordinated, synergistic way.
The researchers say that their design offers a platform approach that could be used across multiple cancer types.
The researchers envision that this platform can be applied to create both therapeutic and preventative regimens, particularly for individuals at high risk for cancer. This is an idea that Atukorale and Kane have turned into a startup called NanoVax Therapeutics.
“The real core technology that our company has been founded on is this nanoparticle and this treatment approach,” says Kane. “This is a platform that Prabhani developed. The startup lets us pursue these translational efforts with the ultimate goal of improving patients’ lives.”
Next, Atukorale and Kane plan to extend this technology to a therapeutic vaccine and have already taken the initial de-risking steps in translation.
Atukorale and Kane credit the Biomedical Engineering department and the Institute for Applied Life Sciences at UMass Amherst, UMass Chan Medical School, and funding from the National Institutes of Health for their support.
The study was published in the October 9 edition of Cell Reports Medicine.
