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Science and tech combine to deliver cancer vaccine innovation

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Scientific and technological innovation is accelerating the development of effective cancer vaccines, report Drs. Daina Vanags, Cori Gorman and Christian K. Schneider of Biopharma Excellence.

Key insights:

When the human papillomavirus (HPV) vaccine was approved, it established the principle that cancer can be prevented, perhaps even treated, by a vaccination. This success followed research which found that 95% of cervical cancers are due to HPV.

Now Merck, one of the leaders in HPV vaccination, is funding the development and worldwide licence of a vaccine candidate to limit Epstein Barr virus (EBV) entry and infection of B cells after it was found that EBV increases the risk of some cancer types. The EBV candidate that Merck is developing in collaboration with ModeX is a nanoparticle vaccine.

Infection with human viruses found in tumours, such as EBV and HPV, are thought to represent the first step in the process leading to the generation of a malignant cell.

Eradicating cancer cells

These developments are important next steps in the journey to better manage, treat and potentially cure cancer. They come as the field continues to witness breakthroughs with advanced immunotherapy treatments, offering clinicians and patients new options that go well beyond the traditional tools of surgery, chemotherapy and radiotherapy. Most notable are breakthroughs in genetically engineered T-cells or chimeric antibody receptor (CAR)-specific T-cell therapies, which utilise known tumour-associated antigens to attract tumour-specific T-cells into the tumours.

While the HPV vaccine and the EBV vaccine candidate are aimed at preventing infection, there is currently extensive research that establishes the potential for therapeutic vaccines to treat many different types of cancer, and potentially eradicate cancer cells. A search of ClinicalTrials.gov shows hundreds of studies into different types of cancer vaccines across all areas.

There is currently promising research into vaccines to induce an immune response against E6 and E7 oncoproteins in advanced cancers of the head and neck. E6 and E7 are the main oncoproteins in high-risk HPV phenotypes. A second area with potential is peptide-based specific, sometimes individualised, tumour vaccines. Advances in high-throughput genomic analysis as well as in epitope prediction “have enabled the design of personalised epitope peptides on the basis of mutations in cancer.”

Despite the promise, there are hurdles to overcome. One of these is the issue of hot vs. cold tumours. Hot tumours are immunogenic, with an abundance of immune cells present, and T-cells can be activated to attack tumour antigens. Cold tumours, are less immunogenic (as an example, pancreatic tumours are typically cold tumours); however, there are strategies to turn cold tumours into hot tumours to make them more sensitive to immunotherapy.  Cold, or non-inflamed tumours, are generally characterised as having a lack of T-cell infiltration, which creates an immunosuppressive microenvironment around the tumour, allowing it to evade immune surveillance.  Inflamed or hot tumours are characterised by high CD8+ T-cell density and increased tumour PD-L1 expression.

Autoimmunity issues

For the vaccine to work, it must break down the body’s natural tolerance of the immune system against “self” structures as they are found in tumours, and that can trigger autoimmunity. This would be achieved either by forcing an immune response against tumour antigens that show similarity with the body’s own structures, or by activating other T-cells as well in the drive to overcome immune system silencing.

Some of the autoimmunity issues facing cancer vaccines can perhaps be solved by using neoantigens, which, due to their underlying mutations, can signal the immune system to target cancer cells without seriously harming non-cancerous cells. As an example, a novel vaccine is being tested to target pancreatic cancer by supercharging the immune system, prompting immune cells to target the cancer cells.

There is also a need to consider tumour progression and giving the vaccine time to work. Often, for cancer vaccines to work effectively, and to be shown to work effectively, they need to be tested on patients with undamaged immune systems. Patients who previously have had chemotherapy treatment may not be suitable candidates.

A further exciting development in cancer vaccine research is the mRNA platform. Some advantages are that mRNA vaccines can be modified more rapidly than protein-based vaccines. Additionally, they may generate more activated T-cells.

AI support

Next in cancer vaccine innovation is the use of novel technologies, such as next-generation sequencing (NGS) optimisation using artificial intelligence, paired with scientific advances in areas such as mRNA or altered peptide ligands with powerful immunoactivators. 

Indeed, with peptide vaccines against RNA viruses, AI has been an important tool in helping to predict components that will produce an immune response, to understand and track the structure of viruses and to assess the value and potential of a vaccine.

AI’s potential in supporting research into cancer vaccines is undeniable and combined with scientific innovation, cancer vaccine therapies will be increasingly effective.

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