Can we develop prophylactic vaccines against cancer

Helmholtz blogs

Headlines such as “First universal cancer vaccination in sight” and statements such as “A vaccine could be developed that can be used against all types of cancer” are examples of what is going wrong in science journalism. The reports are far from the truth set inNature was released.

When most people read of a "universal vaccine against cancer" they think of a prophylactic vaccine, similar to those given to children, to prevent bacterial or viral infections such as measles, diphtheria, and flu. But this is not the case for this cancer vaccine. The study reports on a new variant for onetherapeutic vaccine. This is given to patients to stop and kill cancer cells that are already there. While this vaccination strategy could be “universal” for most cancers, there will not be a universal vaccine that can be given to all patients! The vaccine has to be specific for each type of cancer - so it's a form of personalized therapy.

Although the media is exaggerating the results of the study, the new approach is interesting and could help many cancer patients.

What do the research results show?

Cancer cells acquire mutations in their genetic code (DNA), which allows them to divide and grow uncontrollably. They are derived from normal cells and look just like normal cells to the immune system. This is why there is rarely a strong immune response against cancer cells. The immune system has difficulty distinguishing normal from cancer cells.

The vaccine developed in this study aims to activate the immune system of cancer patients. This should make it possible to fight the cancer from within. The vaccine is directed against so-called neo-antigens. These molecules are regenerated through mutations, are specific to cancer cells and are not made by other cells in the body. Neo-antigens are able to elicit an anti-tumor immune response.

In order to prepare the immune system for the neo-antigen (that's like giving a hunting dog the smell of its prey), pieces of RNA that code for the neo-antigens were packaged in nanoparticles. These small fatty acid coated particles were then injected into tumor-bearing mice or patients. One type of cell of the innate immune system, the dendritic cells, can take up the RNA nanoparticles and initiate a large-scale immune response, including neo-antigen-specific CD8 + T cells. These T cells are able to find and destroy neo-antigen-producing cells and thus fight the tumor.

In mouse models, both prophylactic and therapeutic injections of the RNA nanoparticles resulted in the prevention or regression of several known cancers.

These promising results and a good safety record in primates allowed the method to be transferred to skin cancer patients. Of the three melanoma patients who have previously been treated with the nanoparticles, all three developed strong immune responses against one or two of the four melanoma-specific neo-antigens against which they were vaccinated. In one patient the metastases shrank while in another the cancer stopped growing. The third patient showed no new cancer growth after the surgical removal of the previous metastases.

These results are remarkable, especially since the therapy only causes mild side effects similar to the symptoms of flu. Still, we have to wait for the results from larger studies to see if this effect holds true before we talk about a "breakthrough".

What does the media not tell us?

While the news was quick to write about the good results of this small clinical study, speculating that the procedure would be universally applicable to all cancers, most of them kept silent about the drawbacks.

The "universal" approach will not really work for the fight against all cancers.

In order to be able to vaccinate, the specific neo-antigens of each cancer type must be known. But these are not only different between different types of cancer, but also between different patients suffering from the same type of cancer. Take this study, for example: none of the three melanoma patients reacted to all four neo-antigens against which they were vaccinated. Everyone developed selective immune responses to one or two neo-antigens. They reacted differently due to the different mutations their tumor exhibits. For the success of this type of treatment, it is therefore crucial to know the mutations in each tumor. To achieve this, each tumor has to be checked for mutations (e.g. by genome sequencing) and the vaccination has to be adapted accordingly.

Another problem is the fact that cancer cells are not all created equal. They are heterogeneous within a tumor. For example, some cancer cells can produce neo-antigens while others cannot. So even if we can successfully attack a neo-antigen, that doesn't mean we are able to fight the entire tumor. Resistant cancer cells may remain.

Unfortunately, not all tumors produce neo-antigens. This study vaccinated three melanoma patients against four known antigens. Melanoma is the type of cancer with the highest mutation rate of all cancers, which is why a high number of neo-antigens for melanoma are known. Many of them have been extensively researched to test which can trigger an effective tumor-specific immune response. To test the effectiveness of the new vaccine, the researchers selected well-characterized neoantigens. While this is good news for melanoma patients, it also means that developing a vaccine for other cancers becomes much harder, if not impossible, if effective neo-antigens are not found.

Not all mutations are immunogenic - which means that not all mutations in cancer cells lead to the production of neo-antigens that can be recognized by the immune system. So while all cancer cells have mutations, we will not be able to use all of them in vaccination strategies.

Finally, it remains to be said that this vaccination approachclearly has the potential for success in some types of cancer. However, it will not be a universal cure for cancer. Unfortunately, the study has made the headlines disproportionately inflated without giving a thought that this gives rise to false hope. John Oliver did a great post on science journalism on the subject. If you are interested in where the reporting problems are coming from - click here.

Photo of a patient during vaccination. Flickr.License: CCBY 2.0

Categories: Cancer ResearchTags: Research, Skin Cancer, Immunology, Immunotherapy, Vaccine, Cancer, Melanoma, Science