Scientists have developed a pipeline and ‘plug-and-play’ technology that has the potential to generate cancer vaccines for clinical use.
The innovative pipeline development can be used for identifying, prioritising and evaluating potential tumour antigens for the fast generation of cancer vaccines. The research area of cancer vaccines is in the early stages, but this potential discovery could be game-changing for cancer treatment.
“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 tumour type,” explained first author Sara Feola, Postdoctoral Researcher at the ImmunoViroTherapy Lab (IVTLab), University of Helsinki, Finland.
The report was published in eLife.
A personalised cancer vaccine
The new approach has the prospective to help researchers quickly identify tumour-specific antigens recognised by cytotoxic T cells, generating a powerful, durable, and highly specific response against an individual’s tumour. This could lead to a quicker and easier way to generate effective, personalised cancer vaccines based on the identified antigens.
“Developing personalised cancer vaccines needs several different technologies working together and working fast,” added senior author Vincenzo Cerullo, Professor of Biological Drug Development at the University of Helsinki and group leader at IVTLab. “We need fast and reliable methods to identify and prioritise 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.
“Our research, which builds on previous work, involves developing a novel approach to identify tumour-specific antigens from very small samples, creating a novel algorithm to prioritise 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.”
Investigating the antigen environment of a tumour cell
In the current study, the team investigated the antigen landscape of a tumour cell. They studied a mouse model of colon cancer and used innovative technologies, such as an immunopeptidomics approach based on mass spectrometry analysis, to explore surface antigens on the cell. This generated a list of thousands of peptide candidates and presented a challenge of how to prioritise them.
Moreover, the team used parallel lines of investigation: they looked at the relative amounts of the peptides on cancer cells compared with normal cells; this gave them clues to whether the antigen was tumour specific. They also utilised a software tool to identify tumour antigens that are similar to known pathogen antigens, exploiting their ability to cause a similar immune response to the pathogen antigens.
Adopting these methods resulted in the team having the ability to narrow their candidate list down to 26 antigen candidates. Following this, the team studied the potential of these antigens further by testing how well they stimulated T cells and how effectively they bind to an adenoviral vector that would form the base of the cancer vaccine. All the candidate antigen peptides interacted with the viral vector, but six peptides performed best and were taken forward for further tests.
Controlling tumour growth
Once the researchers developed their technology, they tested to see whether a cancer vaccine carrying the target antigens could stimulate enough of an immune response to control or halt tumour growth. To test this theory, the team used mice with colon tumours on their left and right flanks. They treated one side of the mice with the cancer vaccine coated with each of the candidate peptide antigens. As the team hoped, the cancer vaccine carrying the peptides improved anti-tumour growth in the treated tumour, but one of the cancer vaccines improved anti-tumour growth in the untreated tumours – suggesting that the peptide antigen in this vaccine had mounted a powerful systemic immune response against the tumours.
“We have developed and validated a pipeline that covers for the first time all the stages of personalised cancer vaccine development, starting with isolating peptides from a primary tumour to analysing them to identify the best candidates,” Cerullo concluded. “This pipeline is currently being validated in human cancer patients under our flagship project on precision cancer medicine, iCAN.
“Together, our findings demonstrate the feasibility of applying the pipeline to generate a tailored cancer vaccine by focusing on the prioritisation 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 personalised therapies represent a major goal of successful treatment.”
