When an international collaboration of scientists announced in 2000 that they had sequenced most of the human genome – the so-called blueprint of life – many believed that new, more precise therapies for diseases based on a person’s genetic makeup were close at hand. Treatments have since been developed for some diseases, though the pace of discovery and therapeutic development has not always met those early expectations.

A team of researchers at the University of Arizona Center for Advanced Molecular and Immunological Therapies, or CAMI, hopes to accelerate progress for a range of cancers. They established a collaboration with Quantoom Biosciences, a Belgium-based life sciences technology company, to develop a novel cancer vaccine framework. 

Cancer vaccines are a form of immunotherapy that aims to engage the immune system to attack cancer. The framework, or platform, is based on messenger RNA (mRNA) technology. It promises the ability to create personalized vaccines to treat different types of cancer.

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“Cancer is not a homogeneous disease,” said Ryan Sprissler, associate director of CAMI and a co-leader of the project. “Precision oncology drugs work for a small percentage of patients, and when they stop working, it is nearly impossible to use the same treatment again. The immune system, however, is always working. We need better cancer treatments, and immunotherapies hold tremendous, unrealized promise.”

The path to a cancer vaccine

To create vaccine candidates, CAMI scientists will identify specific mutated tumor proteins called neoantigens, which are unique to each cancer. Neoantigens have the potential to trigger an immune response against cancer, acting like an alarm system that alerts the immune system to the presence of a threat.

Identifying and characterizing the right cancer mutations to use in a vaccine, however, can be challenging. After identifying mutations in a tumor, CAMI scientists will feed them into an artificial intelligence algorithm to select neoantigen candidates most likely to be effective therapeutic targets, said Sprissler, who is a BIO5 Institute member.

“Our hope is that we are able to develop a prediction algorithm that tells us which are most likely to form a stable antigen-presentation complex, which is a set of proteins the immune system can recognize,” he said. “That is what a T cell or T cell receptor identifies in order to activate an immune response.”

Quantoom scientists will then create matching mRNA transcripts for the selected neoantigens. mRNA carries temporary genetic instructions from DNA that tell cells how to make proteins. T cells in the immune system learn to recognize the resulting neoantigen proteins and attack cancer cells that carry them.

When used in a cancer vaccine, mRNA can be delivered into cells to provide instructions for producing one or more cancer neoantigens, allowing vaccines to be individualized for each patient’s tumor.

Microscopic fatty bubbles called lipid nanoparticles will be used to deliver the mRNA. Quantoom’s manufacturing technology uses a self-contained system with microfluidics and robotics to encapsulate mRNA in lipid nanoparticles, allowing the process to be automated.

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“Quantoom could create 10, 20 or more mRNA vaccines specific to the mutations we believe need to be targeted,” Sprissler said. “Tumors are often invisible to the immune system, but through mRNA, cancer mutations can be recognized as foreign antigens, activating an immune response to hunt down and destroy the cells that carry them.”

Researchers will evaluate neoantigens and vaccine candidates in a mouse model to assess the vaccines’ ability to generate an effective immune response against melanoma and to explore their broader therapeutic potential.

Faster progress through partnership 

CAMI and Quantoom each bring specialized expertise to the collaboration. CAMI researchers contribute experience in cancer biology, genetics, immunology and animal models, along with the infrastructure of an academic research institution. Quantoom scientists bring expertise in vaccine technology and development.

“The collaboration fits perfectly with both teams’ experience and goals,” Sprissler said. “CAMI wants to better understand the biology underlying the immune system and cancer while also developing immune-based therapies against disease. Quantoom’s innovative mRNA vaccine technology complements our science and makes this project possible.”

Hala Audi, director of alliances and research and development partnerships at Quantoom Biosciences, said the “next wave of precision medicines” will emerge from industry-academia collaborations.

“What is most exciting in our work with CAMI is the speed of progress and the proximity to patients,” Audi said. “We are laying the groundwork and accelerating the future of precision medicine together. Innovation only matters if it reaches people, and this partnership brings us closer to a future where advanced, life-changing treatments are developed rapidly, safely and with greater impact for patients who need solutions they can afford.”

Molecular characterization of tumors is a fairly routine process, but neoantigen identification, characterization and selection remain difficult.

“There are not many robust tools to do that,” Sprissler said. “There is also the challenge of building high-quality infrastructure to manufacture vaccines quickly enough to treat patients.”

mRNA cancer vaccine clinical trials are underway elsewhere but are expensive and typically rely on proprietary company technology.

“We ultimately need to build vaccine development infrastructure here,” Sprissler said. “Our partnership with Quantoom is helping us do that.”