UMass Amherst researchers create nanoparticle vaccine that prevents cancer in mice
The vaccine also proves highly effective at preventing
cancer’s deadly spread
Not
only did up to 88% of the vaccinated mice remain tumor-free (depending on the
cancer), but the vaccine reduced—and in some cases completely prevented—the
cancer’s spread.
“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 previous research showed that her novel nanoparticle-based drug design can shrink and clear cancer tumors in mice. Now, she’s demonstrated that it can also work preventively.
The first test paired her nanoparticle system with
well-characterized melanoma peptides (called an antigen, similar to how a flu
shot typically contains parts of the inactivated flu virus). The formulation
activated immune cells called T cells, priming them to recognize and attack
this type of cancer. Three weeks later, the mice were exposed to melanoma
cells.
Eighty percent of these “super adjuvant” vaccinated mice
remained tumor-free and survived until the completion of the study (250 days).
In comparison, all of the mice vaccinated with traditional vaccine systems,
non-nanoparticle formulations or unvaccinated mice developed tumors; none
survived longer than 35 days.
The vaccine also protected against the spread of cancer to
the lungs. When exposed to melanoma cells systemically, which mimics how cancer
metastasizes, none of the nanoparticle-vaccinated mice developed lung tumors,
while all of the 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.”
Atukorale describes this 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.”
This first test was conducted using a vaccine with
well-characterized antigens that matched the type of cancer. However,
developing antigens tailored to different cancers requires whole-genome
sequencing or complex bioinformatics screening. So, for the second part of the
study, the researchers used killed cancer cells derived directly from the tumor
mass, called tumor lysate. After vaccination with the nanoparticle lysate
vaccine, the mice were then exposed to melanoma, pancreatic ductal adenocarcinoma
or triple-negative breast cancer cells.
The tumor rejection rates were striking: 88% of mice for pancreatic cancer, 75% of mice for breast cancer and 69% of mice for melanoma rejected tumors. Of these tumor-free, nanoparticle-vaccinated mice, all of them remained tumor-free when the researchers tested if the cancer would metastasize, given systemic exposure.
“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.
