Vaccine trial takes more subtle route

By | Health & Wellness
A new vaccine targets the blood vessels, as shown by the circular shaped structure one above, of tumours, limiting their supply in oxygen and aiding the immune system react more efficiently. Credit image@ Patho, wikimedia commons

Vaccines have aided humanity tremendously ever since their inception, improving immunity to pathogens whilst even sending some strains to the confines of medical history. Wild cases of smallpox have yet to be seen since 1977. And polio, measles and even tape worms could soon follow suit.

Thus, using a vaccine to help treat cancers could be a very potent mechanism for this very common condition, and a trial conducted by the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania have published results that look very promising indeed.

The paper was published in the scientific journal Journal of Clinical Investigation.

Vaccines and cancer have been used in the same sentence before. Indeed, back in 2008, the UK implemented the HPV (human papilloma virus) vaccination programme to combat a virus that could cause certain cancers.

The vaccine being developed by the team targets a vital aspect of tumour health: its blood vessels. Seeing as tumours are extremely metabolically active, particularly due to the rapid and exponential cell division within its structure, they require a good blood supply to ensure that its growing cells receive a steady supply of oxygen and nutrients, which they achieve via tumour angiogenesis: the creation of new blood vessels.

These blood vessels have been the target of studies before, with the idea that removing the vital blood supply would result in an effective treatment for cancer. However, the side effects of these studies resulted in interference with wound healing.

To circumvent this side effect, the team looked into the use of DNA vaccination in order to remove tumour-related blood vasculature. Here, genetically engineered DNA is used to create an immunological response by the host, and whilst they are still only experimentally used, they have the benefit of creating a much wider range of immune responses.

In this case, the vaccine would target a protein known as tumor endothelial marker 1 (TEM1) or endosialin, an over expressed protein common in tumour cells that regular cells rarely produce, which influences blood vessel growth.

The vaccine, dubbed TEM1-TT, was created using a combination of compounds. As DNA is double stranded, the team used one side of the DNA sequence for the TEM1 genes and fused it with the tetanus toxoid (TT), derived from its namesake bacterial species.

In order to investigate the effectiveness of this vaccine, the scientists used mouse models, specifically on mice with breast, colon and cervical cancer.

The results were more than encouraging. As hypothesised, the TEM1-TT vaccine neutralised the endothelial cells that made up the tumour blood vessels, rendering them inert. Reduction in blood flow, and thus oxygen availability, resulted in hypoxia around the tumour. Analysis of the tumours themselves showed the expected reduced vascularisation as well suppressed growth; however the following immune system response was extremely potent.

Whilst the researchers showed increased immune infiltration into the tumour, the murine (mouse) immune system also collected pieces of the tumour cells in a process known as epitope spreading. Here, the immune system used the information gathered by the neutralised tumour cells to mount a secondary response against any remaining cells. Thus the vaccine induced a highly mobilised response, with the immune cells recognising other tumour proteins, increasing the range of the response.

Even more promising is the fact that the scientists were yet to detect any side effects from the vaccine, said Andrea Facciabene, PhD, speaking to the University of Pennsylvania news release.

In addition, the researchers mention how this vaccine could be beneficial for individuals with genes the code for certain types of ovarian cancer, like BRCA1/2 mutations, reducing the chances of contracting the condition.

What other conditions could vaccines be used as a possible therapeutic treatment?


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