UMass Amherst Researchers Develop Promising Nanoparticle Cancer Vaccine

Scientists at the University of Massachusetts Amherst have made significant strides in creating a nanoparticle vaccine that shows promise in preventing various aggressive cancers in mice. This includes melanoma, pancreatic cancer, and triple-negative breast cancer. Depending on the type of cancer, up to 88% of the vaccinated mice remained tumor-free, and the vaccine was effective in reducing—or even entirely preventing—the spread of cancer in the body.

“By engineering these nanoparticles to trigger the immune system through multi-pathway activation in conjunction with cancer-specific antigens, we can effectively halt tumor growth with impressive survival rates,” explains Prabhani Atukorale, an assistant professor of biomedical engineering at UMass Amherst, who is a leading author of the study.

Atukorale had previously demonstrated that her nanoparticle drug design could shrink or eliminate existing tumors in mice. However, these new findings indicate that the method can also prevent cancer from developing from the outset.

In their initial experiment, the research team combined the nanoparticle system with established melanoma peptides, which act as antigens similar to those found in flu shots. This combination activated T cells, training them to recognize and destroy melanoma cells. When the vaccinated mice were later exposed to melanoma, an impressive 80% remained tumor-free throughout the 250-day study. In contrast, all mice that received traditional vaccines or that did not receive any vaccine developed tumors and died within just 35 days.

The vaccine also proved effective in preventing cancer from spreading to the lungs. When the mice were exposed to melanoma cells to simulate metastasis, none of the nanoparticle-vaccinated mice developed lung tumors—while every other mouse did.

“Metastasis remains the biggest challenge in cancer treatment,” says Atukorale. “It’s primarily responsible for the majority of cancer-related deaths, and it complicates our efforts with hard-to-treat cancers like melanoma and pancreatic cancer.”

Atukorale refers to this protective response as “memory immunity,” which is a significant advantage of immunotherapy. “Memory is sustained not just locally but also systemically, which is crucial as the immune system traverses the entire body,” she adds.

The initial phase of testing used a vaccine containing known antigens tailored for melanoma. However, creating specific antigens for each type of cancer can be labor-intensive, requiring extensive genome sequencing or bioinformatics. To streamline the approach, the researchers tested a second version utilizing killed tumor cells, known as tumor lysate, sourced directly from the cancerous tissue. Mice vaccinated with this lysate-based nanoparticle vaccine were later exposed to melanoma, pancreatic ductal adenocarcinoma, or triple-negative breast cancer cells.

The outcomes were noteworthy, with 88% of the mice with pancreatic cancer, 75% with breast cancer, and 69% with melanoma rejecting tumor formation. Moreover, all the mice that remained tumor-free post-vaccination resisted metastasis when exposed to cancer cells.

“The reason behind the survival benefit lies in the tumor-specific T-cell responses we can generate,” says Griffin Kane, a postdoctoral research associate at UMass Amherst and a co-author of the paper. “This formulation leads to intense immune activation of innate immune cells, prompting them to present antigens and prepare tumor-killing T cells.”

This robust T-cell response hinges on the specific design of the vaccine’s nanoparticles.

Vaccines generally include two main components: the antigen, which is a fragment of the harmful pathogen (in this case, cancer cells) that the immune system targets, and the adjuvant, a substance that enhances the immune response to recognize the antigen.

The Atukorale Lab has drawn inspiration from how pathogens stimulate the immune system. For the body to mount a significant immune response, multiple “danger” signals must be triggered through various pathways. “Recent years have highlighted the importance of selecting the right adjuvant, as it provides the second signal essential for properly priming T and B cells,” says Atukorale.

However, many promising adjuvants for cancer immunotherapy tend to not mix well. To tackle this, the Atukorale Lab has engineered a lipid nanoparticle-based “super adjuvant” that can stably encapsulate and deliver two different immune adjuvants together, activating the immune system in a coordinated way.

The researchers believe their design represents a versatile platform that could potentially be applied across different cancer types.

Atukorale and Kane envision that this platform can lead to both therapeutic and preventative strategies, especially for individuals at high risk for cancer. They’ve even initiated a startup called NanoVax Therapeutics around this idea.

“The core technology our company is based on is this nanoparticle treatment approach,” notes Kane. “The startup allows us to pursue these translational efforts to ultimately better patients’ lives.”

Looking ahead, Atukorale and Kane plan to develop this technology into a therapeutic vaccine and have already begun the initial steps towards its translation.

They acknowledge the support from the Biomedical Engineering department, the Institute for Applied Life Sciences at UMass Amherst, UMass Chan Medical School, and funding from the National Institutes of Health.

The findings were published in the October 9 edition of Cell Reports Medicine.