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Last week the term cancer vaccination came up in the news. As vaccinations manipulate the immune system to act against cancer cells, this therapy approach counts as a form of cancer immunotherapy – although the mechanism of action is very different to the checkpoint inhibitors we reported about here.
We discussed the basic biology behind vaccination in a previous blog post, but in short: vaccinations aim to introduce a pathogen to the immune system in way that does not induce disease. This makes the immune response stronger and faster when a person encounters the actual pathogen, preventing life-threatening diseases.
But how can we vaccinate against cancer?
Most of you are actually aware of the first way: the vaccination against viruses that can cause cancer such as the HPV vaccination. This approach resembles a classical vaccination where parts of the pathogen are injected into a person to enhance the immune response against the pathogen and thereby prevent infection and the subsequent development of cancer. The second type of cancer vaccine, the one you may have read about this week is quite different – it’s based on immune cells being shown cancer-specific, mutated proteins in the lab and then re-infusion of these cells into the cancer patients. A cellular vaccine. This approach is a form if personalised treatment, as the mutated cancer-specific proteins are different in each cancer patient.
The human papillomavirus (HPV) is best known for causing cervical cancer in women. The sexually transmitted virus infects skin or mucosal surfaces and is subclinical, which means it causes no symptoms in most infected people. However, HPV16 and HPV18 (two of more than 40 types of HPV) cause around 70% of all cervical cancer cases.
Given this link, Nobel Prize winning research by Harald zur Hausen lead to the development of a HPV vaccine, which is now as a standard given to girls aged 11-14 around the world. Two vaccines are available: Gardasil and Cervarix. Both protect against the initial infection with HPV16 and 18, preventing cancer. Gardasil also protects against HPV types 6 and 11, which cause 90% of genital warts. As the vaccination only protects from the first infection with HPV, it is important that the vaccination is given to young girls before they have sex for the first time.
A less known fact about HPV is that the virus not only infects men and women alike, but that it also causes cancer in men. HPV is the leading cause of mouth and throat cancer in men and can also cause penis or anal cancers and genital warts. A clinical trial has shown that the vaccination of men against HPV can prevent analcarcinoma and genital warts and Gardasil has clinical approval for usage in boy and girls. But while boys are routinely vaccinated in the USA and Australia, in Germany and the UK only girls are vaccinated. To me personally this makes little sense and hopefully the vaccination guidelines will change soon.
Personalised cancer vaccinations
Personalised vaccinations directed against mutations specific for a certain tumour are not approved for clinical use yet, but a lot of research is trying to develop this field to help patients. Researchers from the University of Washington now published results showing promise in melanoma patients.
In the study, the cancer genome was sequenced in three melanoma patients. This means biopsies of the tumour were analysed for mutations in the DNA. These mutations lead to the formation of mutated proteins (called neoantigens), which are only present in the cancer tissue. In theory neoantigens can be used in vaccinations to activate the immune system to specifically recognise and destroy cancer cells.
The vaccination process used is different to the “normal” vaccinations we talked about so far. Rather than injecting the identified neoantigens into the patients, immune cells are taken from the blood of patient, differentiated into so called antigen-presenting cells (APC) and exposed to the proteins in the lab. APC are highly specialised immune cells, which take up proteins from pathogens and present them to other immune cells, called T cells, to activate them. Once the APCs have taken up the patient-specific neoantigens they are infused back into the patients, where they hopefully induced T cells specific for the cancer cells. Indeed, in this study, tumour-specific T cells were found in the blood of the three melanoma patients two week post vaccination.
Similar trials using cancer-associated rather than cancer-specific antigens (cancer-associated antigens are expressed in non-cancer cells as well but at a lower level) have all failed to mount success in large trials. However given that the new approach uses antigens only found in the tumour and nowhere else and that the vaccine was based on seven antigens rather than only one, as done previously, lets the researcher be optimistic about their approach. And we will keep you up to date with further results in this area.
Due to the complex procedures need in this therapy and the fact that the vaccines must be different for each patient, the approach is costly. For a long time pharmaceutical companies did not want invest in these personalised approaches. But not only are the methods surrounding the therapy becoming better and cheaper, it also seems that the pharma industry is more willing to spend money on the new therapy approaches as described in this post on the Nature website.
If you have any questions on this topic please feel free to contact us.