New discovery likely to result in cancer vaccine development

According to research published in eLife, researchers have developed a pipeline for detecting, prioritizing, and testing potential tumor antigens for the rapid development of cancer vaccines.

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The novel method will help researchers swiftly discover tumor-specific antigens that cytotoxic T cells recognize, resulting in a potent, long-lasting, and highly targeted response against a patient’s tumor. As a result, efficient, customized cancer vaccines based on the appropriate antigens could be developed faster and more easily.

For a cancer vaccine to be effective, we need to select target antigens that elicit a strong immune response, are exclusively present on cancer cells and are tailored to an individual’s unique tumor type.”

Sara Feola, Study First Author and Postdoctoral Researcher, ImmunoViroTherapy Lab (IVTLab), University of Helsinki

“However, only a few, if any, of the antigens on a tumor meet those characteristics, making it very difficult to identify and prioritize potentially effective candidates. Our pipeline comprises all the essential steps for the optimal development of a therapeutic cancer vaccine, but which could be carried out much more quickly on an individual patient basis, enabling true personalized therapy,” she explains.

Developing personalized cancer vaccines need several different technologies working together and working fast.”

Vincenzo Cerullo, Senior Author and Professor, Biological Drug Development, University of Helsinki

Cerullo was also a group leader at IVTLab. “We need fast and reliable methods to identify and prioritize antigens, as well as rapid, inexpensive and feasible approaches to deliver these antigens to patients. During the past six years, we’ve been working on a project supported by the European Research Council (ERC) to make all the pieces of this complex puzzle work together, creating the pipeline that has been partially described in this work,” he adds.

Cerullo further states “Our research, which builds on previous work, involves developing a novel approach to identify tumor-specific antigens from very small samples, creating a novel algorithm to prioritize peptides based on their similarity to pathogen-derived peptides, and building several different plug-and-play technologies to deliver these peptides together with viruses or bacteria that kill cancer cells.”

The researchers started by looking at the antigen landscape of a tumor cell, or all of the various peptides on the cell surface. They looked at a mouse model of colon cancer and then used cutting-edge technology to investigate surface antigens on the cell, including an immunopeptidomic method based on mass spectrometry evaluation.

This resulted in a database of thousands of peptide possibilities, with the task of prioritizing them posing a challenge.

The researchers looked at the relative amounts of peptides on cancer cells against normal cells in two ways. First, they examined the relative amounts of peptides on cancer cells versus normal cells. This helped them figure out if the antigen was genuinely tumor-specific.

Next, researchers employed a software tool built in their lab to detect tumor antigens that are related to known disease antigens, allowing them to leverage their potential ability to elicit an immune response identical to the pathogen antigens.

Using these strategies, the team was able to reduce the number of antigen participants from thousands to only 26. They then investigated the antigens’ potential by seeing how well they activated T cells and how well they bound to an adenoviral vector, which would serve as the vaccine’s foundation. Although all of the prospective antigen peptides linked with the viral vector, six of them outperformed the others and were chosen for further testing.

The next step was to explore if a vaccination containing these antigens could elicit a strong enough immune response to slow or stop tumor progression. The researchers utilized mice with colon tumors on their left and right flanks to test this. The mice were subsequently given a vaccine that was coated with each of the potential peptide antigens on one side.

They discovered that vaccines containing the peptides boosted anti-tumor development in treated tumors, but one of the vaccines also enhanced anti-tumor growth in untreated tumors, implying that the peptide antigen in this vaccine elicited a significant systemic immune response against the tumors.

We have developed and validated a pipeline that covers for the first time all the stages of personalized cancer vaccine development, starting with isolating peptides from a primary tumor to analyzing them to identify the best candidates. This pipeline is currently being validated in human cancer patients under our flagship project on precision cancer medicine, iCAN.”

Vincenzo Cerullo, Senior Author and Professor, Biological Drug Development, University of Helsinki

He also added, “Together, our findings demonstrate the feasibility of applying the pipeline to generate a tailored cancer vaccine by focusing on the prioritization and selection criteria and adopting quick plug-and-play technology, called PeptiCRAd, through decorating a clinically approved adenovirus vector with the selected peptides.”

“This opens up the possibility of rapidly generating vaccines for clinical use, where effective personalized therapies represent a major goal of successful treatment,” Cerullo concluded.