Scientists Close In on a Universal Cancer Vaccine
By University of Massachusetts Amherst
A research team at the University of Massachusetts Amherst has shown that a nanoparticle-based vaccine can successfully prevent melanoma, pancreatic cancer, and triple-negative breast cancer in mice. Depending on the cancer type, as many as 88 percent of vaccinated mice remained free of tumors (depending on the cancer), and the approach reduced—and in some instances entirely blocked—the spread of cancer in 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’s earlier
work found that her nanoparticle-based drug design could shrink or
eliminate existing tumors in mice. The new results reveal that the same
technology also works as a preventative strategy.
Testing the Vaccine with Melanoma Antigens
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 shot typically contains parts of the inactivated flu virus). This combination activated T cells, which were then primed to recognize and destroy melanoma cells. Three weeks after vaccination, the mice were challenged with melanoma.
Eighty percent of the mice given this “super adjuvant”
nanoparticle vaccine remained tumor-free and survived for the entire 250-day
study. Every mouse that received a traditional vaccine, a non-nanoparticle
formulation, or no vaccine at all developed tumors, and none lived beyond 35
days.
The vaccine also prevented melanoma from spreading to the
lungs. When the mice were systemically exposed to melanoma cells in a way that
mimics metastasis, none of the nanoparticle-vaccinated mice formed lung tumors,
while all other mice 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.”
Long-Lasting Immune Memory Across the Body
Atukorale refers to this protection as “memory immunity.”
“That is a real advantage of immunotherapy, because memory is not only
sustained locally,” she says. “We have memory systemically, which is very
important. The immune system spans the entire geography of the body.”
The first round of testing used antigens designed
specifically for melanoma. Developing customized antigens for every cancer
type, however, often requires whole-genome sequencing or advanced
bioinformatics. To address this challenge, the researchers conducted a second
experiment using killed cancer cells from the tumor itself, known as tumor
lysate. Mice vaccinated with this nanoparticle lysate formulation were then
exposed to melanoma, pancreatic ductal adenocarcinoma or triple-negative breast
cancer cells.
High Tumor Rejection Rates Across Multiple Cancers
The results were striking. Tumor rejection was seen in 88
percent of pancreatic cancer cases, 75 percent of breast cancer cases, and 69
percent of melanoma cases. Every vaccinated mouse that remained tumor-free also
resisted metastasis when later 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.”
How the Nanoparticle Vaccine Creates a Strong Immune
Response
This powerful T-cell activation is possible because of the
unique nanoparticle structure used in the vaccine.
Vaccines—regardless the target disease—include two main
components: the antigen and the adjuvant. The antigen represents the part of
the pathogen (in this study, cancer cells) that teaches the immune system what
to attack. The adjuvant stimulates the immune system so that it recognizes the
antigen as a threat and mounts a strong response.
The Atukorale Lab designs its vaccines to mimic how
pathogens naturally alert the immune system. Effective immune activation
requires several “danger” signals working 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.
Many promising adjuvants used in cancer immunotherapy do not
combine well at the molecular level, similar to how oil and water separate. To
address this limitation, the team created a lipid nanoparticle “super adjuvant”
that can encapsulate and deliver two different immune-stimulating ingredients
in a stable and coordinated way.
Toward a Broad Cancer Vaccine Platform
The researchers believe this nanoparticle system offers a
flexible platform that could be adapted to many cancer types.
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 for a startup launched by Atukorale and Kane, 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.
Reference: “Super-adjuvant nanoparticles for platform cancer
vaccination” by Griffin I. Kane, Tiana E. Naylor, Ellis F. Lusi, Meghan L.
Brassil, Kim Wigglesworth, Ronnie W. Dinnell, Miranda B. Diaz-Infante, Leah M.
Whiteman, John Lukas, Megan Winkler, Rohini Josh, Julia Cerrutti, Haruka Mori,
Stefania Gallucci, Katherine A. Fitzgerald and Prabhani U. Atukorale, 9 October
2025, Cell Reports Medicine.
DOI:
10.1016/j.xcrm.2025.102415

