Therapeutic cancer vaccines have not yet lived up to expectations in terms of their effectiveness, but research is still ongoing, experts say. Currently, research into cancer vaccines is also underway in Poland.
Experts spoke about this at the seventh expert debate of the Polish Science Foundation, which was held as part of the “Let’s trust science” series. prof. Maciej Zylic, biochemist, molecular biologist, president of the Polish Science Foundation, recalled that work on cancer vaccines has been going on for several decades. As he explained, this is not about preventive vaccines against the HPV or HBV viruses that contribute to the development of cancer, but about curative vaccines that should make our own immune system recognize cancer as something foreign and attack it.
How does the cancer vaccine work?
prof. Zhilich noted that initially they were looking for changes (mutations) in the genes of cancer cells that would distinguish them from healthy cells. “They were looking for changes in the genes that would be typical for all types of cancer. However, it turned out that cancers are very different from each other (…) so it is almost impossible to find a vaccine that would work for all types of cancer,” the specialist explained.
We now know that a therapeutic cancer vaccine needs to be more personalized—not just by type of cancer, but by cancer patient. One of the promising options for cancer vaccines is vaccines based on mRNA technology used to create a vaccine against the SARS-CoV-2 virus, recalled prof. Zhilich.
“This technology was originally intended to fight cancer, but from the point of view of an mRNA vaccine, cancer is a much more difficult adversary than viruses,” said Prof. Jacek Gemelity from the Center for New Technologies at the University of Warsaw.
As experts explained, to create an mRNA vaccine, the DNA of cancer cells and healthy cells of a given patient is sequenced and those elements are searched for that most distinguish these cells from each other. “About 20 different genes are selected in this way, and then this genetic information is transcribed into mRNA and injected into the patient,” explained Prof. Zhilich.
Protein fragments (peptides) are created in cells based on mRNA, and immune cells learn to recognize them as foreign antigens in order to recognize and attack cancer cells.
prof. Gemility has calculated that mRNA can be very effective, since a dozen or several dozen antigens can be encoded in one of its strands. “These fragments do not have to be long, and they can also occur in several variants in case of additional mutations,” he explained.
prof. Jacek Jassem stressed that mRNA vaccines are well tolerated, easily degraded, do not integrate with the host’s genome, and are not infectious. “In addition, they stimulate both humoral and cellular immunity, are quite simple to manufacture, and their production is inexpensive,” he listed.
How does cancer vaccine research work?
As reminded by prof. Zhilich, research is currently underway on peptide cancer vaccines - instead of introducing mRNA containing the peptide recipe into cells, only peptides characteristic of cancer cells are introduced. Then they must be recognized as foreign by immune cells, and due to this, cancer cells will be attacked and destroyed.
prof. Krzysztof Yiannopoulos, hematologist, head of the Department of Experimental Hemato-Oncology at the Medical University of Lublin, who worked in Germany on peptide vaccines for one of the types of leukemia, emphasized that the most immunogenic part of the protein (the most immunogenic peptide) is administered, which consists in stimulating the reaction of cytotoxic lymphocytes that destroy tumor cells. cells. “In cancer, where, apparently, this mechanism of antigen processing is impaired, there may be a certain advantage of peptide vaccines (over mRNA vaccines - PAP),” said Prof. Yiannopoulos.
He recalled that in the case of cancer vaccines, the problem is, among other things, that the antigens on cancer cells are best known to the body, because cancer occurs in our own cells. Therefore, the immune system may not recognize them as foreign.
“Mutations that lead to new antigens are relatively rare,” the hematologist said. Therefore, it is most often based on the fact that the expression of this antigen is low on normal cells and significantly higher on cancer cells. “But it’s still the same antigen,” he said.
In his opinion, vaccines in the treatment of cancer will be used at some stage of therapy, but this will not be such a breakthrough, as is the case, for example, with antiviral vaccinations.
prof. Jamiality recalled that work is also underway on cell-based cancer vaccines. These involve harvesting cytotoxic T cells, which are then genetically engineered to recognize cancer and re-injected into the patient.
prof. Natalia Marek-Trzonkowska, director of the International Cancer Vaccine Research Center at the University of Gdansk, is working on a new lung cancer therapy that uses knowledge of the role of regulatory T-lymphocytes. These are immune cells that cause immune tolerance, so they play a negative role in the development of cancer. “Very often, cancers even lure these cells into their territory and, for example, in lung cancer, we see a lot of regulatory T cells, which undoubtedly contribute to the tolerance of this cancer and weaken the effect of cytotoxic therapy. This knowledge can be used to develop effective therapies that break this immune tolerance,” he said.
She added that her team has developed an algorithm to identify cancer-recognizing cells. “We can isolate them from a patient’s blood, sort them using special devices, and multiply them in a test tube to return these cells to patients. (…) For each patient, we select different cells - whole clones of cytotoxic and helper T-lymphocytes, because these two types of cells work together and their presence is necessary for the success of therapy, ”she explained.
She added that it is now necessary to develop personalized cancer vaccine therapies. “Cancers change a lot. They are different at different stages of cancer and you need to respond quickly,” she said.
According to prof. A huge problem in the case of cancer is also their heterogeneity. “Cancer is certainly a very difficult adversary because it has developed mechanisms that put our immune systems to sleep. Therefore, cancer vaccines are combined with checkpoint inhibitors (drugs that make cancer more visible to the immune system - PAP), the specialist said.
prof. Jassem stressed that due to the difficulties in developing cancer vaccines, progress in this area is very modest. “In addition to the BCG vaccine (tuberculosis vaccine used in bladder cancer immunotherapy - PAP), two more therapeutic cancer vaccines are registered - one for the treatment of prostate cancer and the other for melanoma,” said Prof. jass
He added that a vaccine against disseminated prostate cancer (Sipuleucel-T) had been high hopes for some time. However, it is inconvenient to manufacture and use. In addition, there is a new hormonal therapy for prostate cancer that is more effective and easier to administer (oral). The same thing happened with melanoma, in the treatment of which effective immunocompetent drugs have been developed.
“However, there is still interest in cancer vaccines, with more than 1,000 clinical trials currently underway,” concluded Prof. yass He added that vaccines have a number of advantages and there are good chances to use them, maybe not in monotherapy, but together with other cancer treatments.
Source: Wprost
