How does immunotherapy against cancer work?

In the first blog entry about cancer immunotherapy, I guided you through the ins and outs of how our own immune system can help us fight cancer and the strategies that are used to help and improve this system in that fight. In this second entry, I am going to explain vaccines based on tumor proteins and those vaccines used against cancer-related viruses.

But before we start, what is a vaccine? According to the World Health Organization, a vaccine is:

“any preparation intended for generating immunity against a disease by stimulation of antibody production. For example, this may be a suspension of dead or attenuated microorganisms, or products or derivatives from microorganisms. The most common method to administer vaccines is by injection, although some may be administered orally or by using a nasal spray”.

And, how is this applied to cancer? First of all, there are two main types of cancer vaccines, those that help prevent it and those that help treat it once it has appeared. Vaccines that help prevent cancer generally focus on training the immune system to recognize viruses that cause certain types of tumors. Therefore, there are vaccines against human papillomavirus, which may cause anal or cervical cancer, or hepatitis C virus, which may lead to hepatic cancer. Similarly to vaccines that are used to treat infectious diseases, this type of vaccines is based on an antigen that is part of the structure of the virus. As explained in the previous blog entry, an antigen is a molecule that is able to promote an immune reaction. However, since the antigen in the vaccine is only a part of the virus, it cannot infect anymore. Thus, after an individual is vaccinated with these viral antigens, the immune system of that person can recognize them and “memorizes” that information. By doing so, when our immune system encounters the real virus, it can rapidly react thanks to the information it previously stored, thus eliminating the virus. However, a problem of this type of vaccines is the large amount of different populations of a same virus, which may have variations in the antigens they carry. Something similar occurs with the flu vaccine, which must be reformulated from time to time to adapt to these antigen changes.

With regard to vaccines based on tumor antigens, they are generally based on proteins that are only or mainly found in tumor cells. These proteins, or small pieces of them called peptides, are used in a similar way as the antigens in vaccines against cancer-related viruses: they would train the immune system to recognize molecules that are usually present in the tumor so that it can react against them whenever our immune system encounters those same molecules in a cancer cell.

An alternative to this form of vaccine relies on dendritic cells, a highly specialized kind of immune cells. These cells are in charge or “presenting” foreign objects or molecules to other components of the immune system, such as lymphocytes, the cells that we described in the previous entry. In cancer treatment, cells that can differentiate into dendritic cells are isolated from a cancer patient, loaded with cancer antigens (either by exogenously adding the peptides or by genetic modification to endogenously express the protein), and administered to the patient. Therefore, dendritic cells train the immune system to recognize that tumor-associated protein as “foreign” and to induce an immune response to it. The main challenge with this form of therapy is to find the proteins that are expressed in tumor cells but not in healthy cells. Our immune system is trained to “ignore” cellular components that are part of our own body, which include proteins that, in spite of being mostly expressed in tumor cells, are also expressed in healthy tissues. Thus, when we use those self-antigens in cancer immunotherapy, it is possible that our organism does not identify them as foreign.

To improve the efficacy of this type of immunotherapy, cancer vaccines are administered in combination with adjuvants. Adjuvants are compounds that stimulate the immune system and improve the quality and duration of an immune response to an antigen. Although other forms of immunotherapy may be more popular to cancer vaccines nowadays, they remain an important and helpful strategy to wake up and alert our body to the presence of tumor cells.