Cancer vaccines
Anna Petrenko, Copper News
Prevent, overcome, reassure
At the mention of the word "vaccine", most people immediately think of measles, chickenpox or flu. In these vaccines, weakened, killed microorganisms or molecules typical of them are used to trigger the immune response of the body. After the vaccine enters the body, the immune system learns to respond to such an "irritant" in training mode, remembers the pathogen and, when confronted with a real infection, quickly wins. Some anti-cancer vaccines work on a similar principle, but you have to fight with your cells already.
Scientists have long been developing vaccines that could prevent or cure cancer. One of the first experiments belonged to William Kohli with his "toxins".
Others have tried to trigger the immune system's response to tumors by using the Bacille Calmette–Guerin bacillus (BCG) to prevent tuberculosis. This is a live attenuated vaccine with a rich composition, and it would be surprising if it did not have a strong effect on the immune system as a whole. However, since 1935, most attempts to treat her cancer have shown disappointing results. Despite this, when processing the data of all published reports, it became clear that if BCG was administered at a very early age or vaccination provided powerful protection against tuberculosis, then the vaccine prevented leukemia.
Preventive cancer vaccines
A small part of oncological diseases are caused by viruses. Therefore, vaccines that protect against these viruses can also be used as anti-cancer. They are not aimed at cancer cells, but specifically at infection.
Since the 1970s, it has become clear that the human papillomavirus (HPV, or HPV) can lead to cell malignancy. This problem was dealt with by Harald zur Hausen and his colleagues. In a 2001 interview, he stated that the prospects for cancer vaccines are promising: "There are now 10 million cases of cancer a year worldwide. In the future, it should be possible to prevent 1.25 million of them with vaccination."
HPV is the most common viral infection of the genital tract. In total, more than 100 types of this virus are known, and at least 13 of them can lead to cancer pathology. It is associated with cancer of the cervix, anus, vagina, penis and some others. Now there are two approved preventive vaccines against several types of HPV: Gardasil (approved by the FDA in 2006) and Cervarix (approved in 2009). Both include a virus-like particle of the recombinant capsid protein L1. The Advisory Committee on Immunization Practices of the USA (The Advisory Committee on Immunization Practices of the US CDC) recommends routine vaccinations for girls and boys aged 11-12, but it is possible to vaccinate a child from the age of 9. Those who were not vaccinated at an early age can be vaccinated later.
Unfortunately, HPV anti-cancer vaccinations are the only ones of their kind. For example, patients with chronic hepatitis B virus (HBV, or HBV) have an increased risk of liver cancer. But a vaccine against HBV has not yet been developed.
In addition, most types of cancer are not caused by viruses. Doctors are not yet sure whether it is possible to create preventive vaccines for them. There are already some developments, but they are in the early stages, and it's too early to talk about the results. In addition, it is believed that even with success, it will take a long time before being introduced into routine clinical practice.
Cancer-fighting vaccines
The purpose of cancer vaccines differs from both conventional and preventive antitumor, fighting viruses. Inoculation of such a mixture should show the immune system how to overcome an existing disease. Unfortunately, the vast majority of such developments are at various stages of clinical trials and are not yet widely used. Because of this, curing cancer with a simple vaccination is still a matter of the future.
Researchers use several strategies for the vaccine's action.
The first option is cancer cell vaccines. The tumor cells removed during surgery are changed in the laboratory and injected into the patient. Immune cells react not only to the injected vaccine with the killed cancer cells, but also to similar ones – that is, to cancer cells remaining in the body. If the vaccine is administered to the same patient whose tumor was cut out, it is called "autologous". If the "donor" and the recipient of cancer cells are different people, then this is an allogeneic vaccine.
Researchers from Thomas Jefferson University in 2014 conducted clinical trials of a similar vaccine on 12 patients with recurrent glioblastoma. The participants' cancer cells were treated in the laboratory with AS-ODN, which turns off the IGF-R1 receptor. It has been shown that this receptor stimulates the growth and metastasis of the tumor, and its blocking can lead to its self-destruction. Half of the patients had an immune response to the vaccine. Scientists explain this by the fact that the rest of the immune system could have been weakened by previous chemotherapy. The next stage of clinical trials is being conducted in 2015.
The second type is vaccines with antigens. To stimulate the immune system, they use not whole cancer cells, but one or more antigens, proteins or peptides. These vaccines are not made for a specific patient, but against a certain type of cancer.
In America, in 2014, studies were conducted on the safety of a vaccine against breast cancer. The development of scientists from the Washington University School of Medicine "trains" white blood cells for mammaglobin-A. This protein is expressed almost exclusively in the mammary gland, and in 40-80% of tumors its level is abnormally high. In half of the 14 women with metastatic breast cancer and a high concentration of mammoglobin-A, the cancer did not progress within a year after vaccination (there were significantly fewer such outcomes in the control group). The side effects were minor. The research is planned to continue.
One of the strategies is gene vaccines. They cannot be attributed to a separate type, but to create them, vectors are needed – nucleotide sequences that are inserted into someone else's genome. Thus, using the target cell's own enzyme apparatus, scientists force it to produce the desired protein. DNA fragments of viruses, bacteria, and yeast cells are often used for this. The use of such vaccines allows not only to force the cell to produce additional tumor antigens, but also to cause an increased immune response, since the gene material is taken from, for example, bacteria. In addition, their production is easier and cheaper.
A phase II clinical trial of Prostvac-V/F was already conducted at the end of 2014 for patients with prostate cancer resistant to hormone therapy. Prostvac-V is based on the cowpox virus and modified to produce PSA (prostate-specific antigen) and three other proteins noticeable to the immune system (a triad of costimulating molecules – TRICOM). Prostvac-F is also made from chicken pox virus. It contains the same genetic material, but is injected several times.
Finally, the most successful, perhaps, are vaccines using dendritic cells. These cells help the immune system to "see" the tumor. They destroy cancer cells and expose their "pieces" on their surface. T cells recognize antigens and begin an immune reaction against the cells containing them.
Sipuleucel-T (Provenge) for the treatment of prostate cancer is the only one that has received FDA approval. It is used for those patients who are not helped by hormone therapy.
The principle of its operation is as follows: cells of the immune system are isolated from the patient's blood and transformed into dendritic cells, treating them with a special mixture of molecules. In addition, newly appeared dendritic cells are presented with prostatic acid phosphatase (PAP). Then they are injected back into the patient several times intravenously, which causes the body's response to the tumor. Despite the fact that the vaccine does not cure prostate cancer, it prolongs the patient's life by an average of several months.
Other vaccines with dendritic cells are also being actively investigated. Nature Reviews Cancer writes that this year Mitchell, Batich and colleagues showed that the response to the vaccine in patients with glioblastoma can be enhanced by pre-conditioning with Td toxoid (tetanus/diphtheria – tetanus/diphtheria), an antigen that causes a strong reaction of the body.
The prospects
With the improvement of scientific technology and the accumulation of knowledge, it turned out that the immune system is much more complex than expected, and cancer cells are "smarter" in disguise. But despite this, there are more and more successful developments of cancer vaccines. There is an increasing preference for personalized vaccines – aimed at mutations of a particular patient. So, recently, American scientists reported on successful clinical trials of a vaccine against melanoma.
Progress does not stand still. For example, scientists have created a three-dimensional self-assembling structure for "training" immune cells. In the experiment on mice, tumor proteins were loaded into the pores of the structure, which had to be presented to the immune system, and then received a powerful response from the body.
Scientists themselves have high hopes for vaccines. "In recent years, researchers and the public have begun to realize the role that the immune system plays in the prevention and treatment of cancer," says Craig Hooper, professor in the Department of Cancer Biology at Thomas Jefferson University. Esteban Celis, professor of the immunology program at the Moffitt Center (Moffitt's Immunology Program), believes that such vaccines are a good alternative to traditional treatments that lead to serious side effects and are often useless in the later stages of the disease.
Immunotherapy of oncological diseases topped the ranking of the most significant scientific achievements of 2013, compiled by the journal Science and published in its December 20 issue. The top 10 also includes seven more discoveries in the field of medicine, genetics and biology.
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25.05.2015