Small but mighty: nanoparticle vaccine prevents cancer in mice

A lipid nanoparticle-based vaccine prevented tumor formation and metastasis in the majority of treated mice.

Researchers from University of Massachusetts (UMass) Amherst (MA, USA) have created a nanoparticle-based cancer vaccine that effectively prevented cancer in mice. The vaccine generated tumor-specific T-cell responses and could lead to both therapeutic and preventive treatment regimes.

Vaccines contain two major components, the antigen and the adjuvant: the antigen is the part of the pathogen your immune system is being trained to recognize, while the adjuvant activates the immune system to become trained. Modern vaccines often use virus subunits, which mitigate the risk of infection but reduce the effective adjuvanticity.

Float like a butterfly, STING like a nanoparticle

This study – led by Prabhani Atukorale, corresponding author and assistant professor of biomedical engineering (UMass Amherst) – reported the development of a ‘super-adjuvant’ vaccine based on her previously designed nanoparticle system that can work preventively. Her team utilized lipid-based nanoparticles to encapsulate agonists of the stimulator of interferon genes (STING) and Toll-like receptor 4 (TLR4) pathways, both critical components in the innate immune response.

The vaccine was tested first with cancer-matched antigens, followed by a vaccine that leveraged tumor lysate as the antigen. Mice were treated with the tumor lysate version before being exposed to melanoma, pancreatic ductal adenocarcinoma or triple-negative breast cancer cells. Once exposed, the mice were systematically exposed to further cells to simulate metastasis.

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Easy as ABC: polymer increases chemotherapeutic payload

Bottlebrush-shaped polymer chains can deliver hundreds of prodrug molecules directly to tumors, rather than the handful currently possible with antibody–drug conjugates (ADCs).

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Boosting the innate immune response

The team found that a significant proportion of the mice treated with the vaccine did not develop tumors: 88% of mice for pancreatic cancer, 75% of mice for breast cancer and 69% of mice for melanoma. The vaccine led to a significant boost in polyfunctional CD8+ T cells, CD4+ T cells, CD19+ B cells and plasma IgG antibodies, demonstrating a broad immune response. Additionally, all of the mice that didn’t develop tumors remained tumor-free after exposure to further tumor cells.

“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,” explained Atukorale.

“The tumor-specific T-cell responses that we are able to generate – that is really the key behind the survival benefit,” commented Griffin Kane, postdoctoral research associate and first author (UMass Amherst). “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.”

Future applications

The researchers hope that this platform could be used to develop vaccines across multiple cancer types and have already formed a startup to extend the technology.

“Metastases across the board is the highest hurdle for cancer,” noted 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.”