The Covid-19 vaccine developed by Oxford University in partnership with pharmaceutical company AstraZeneca could facilitate the creation of an immunizer against cancer.
In tests conducted in mice, the vaccine candidate was able to increase levels of cancer-fighting cells and improve the effectiveness of treatment against the disease. The results were published in the journal Journal for ImmunoTherapy of Cancer.
The Oxford/AstraZeneca vaccine against the new coronavirus uses a technology called a non-replicating viral vector, which aims to induce the immune system’s response and generate protection against the disease. The immunizing agent is based on a genetically modified chimpanzee adenovirus, which is unable to harm humans, with a gene for the protein S (Spike) of the new coronavirus.
Based on the knowledge acquired in the creation of the vaccine that has been widely used in Brazil, researchers from Oxford are working on the development of an immunizing agent that aims to treat cancer. The vaccine candidate, which is still in the pre-clinical testing phase with the participation of animals, also uses viral vector technology with an initial two-dose regimen.
Vaccine + immunotherapy
According to the study, the vaccine showed positive results when used in combination with immunotherapy, which is a method of treatment against cancer based on the induction of the fight against cancer cells by the patient’s own immune system. Treatment is different from chemotherapy and radiotherapy techniques, for example, which directly attack tumor cells.
Although promising, treatment with immunotherapy may have low efficacy for some patients, especially those with low levels of tumor-fighting cells in the body.
“Immunotherapy will only work if the patient has the correct immune system cells, in this case they would be the CD8+ cells, which really attack the tumor and defend our organism. In cancer patients, these cells are often reduced by the action of the tumor”, explains Bryan Eric Strauss, Research Coordinator at the Viral Vectors Laboratory of the Center for Translational Research in Oncology (CTO) of the Cancer Institute of the State of São Paulo (Icesp ).
It is in this context that the Oxford vaccine technology enters, which generates strong responses from specific defense cells in the body, called CD8+ T lymphocytes, which are necessary for good effects against tumors.
From experience with the Oxford/AstraZeneca immunizer, researchers have developed a potential two-dose therapeutic cancer vaccine with different primary and booster viral vectors, including the Covid-19 vaccine vector.
Preclinical trials in mice demonstrated that the vaccine increased levels of CD8+ T cells, which infiltrate the tumor, and amplified the response to immunotherapy. The combined vaccine and immunotherapeutic treatment resulted in a greater reduction in tumor size and improved animal survival compared to immunotherapy alone.
“If you stimulate the immune system and increase CD8+ cells, freed from the inhibitory effect triggered by the tumor, thanks to the action of immunotherapy, there will be a greater effect against the disease”, explains researcher Luiz Fernando Lima Reis, director of Education and Research at the Hospital Sírio-Libanês, in São Paulo.
The vaccine prescription
Vaccines can be produced using different technologies. However, the objective is the same: to present to the immune system information associated with the harmful agent to the body, which can be a virus, a bacteria and even a tumor, so that the defense system produces cells and specific antibodies for the fight against that agent.
To formulate the immunizer specifically targeted at tumor cells, the researchers focused on two proteins that are present on the surface of different types of cancer cells, called MAGE.
“The antigen is the bait that shows the immune system how to attack the tumor. It is similar to what is done in the Covid-19 vaccine, which uses the Spike protein as the information the immune system needs to find the target and get rid of the coronavirus. In the case of cancer, this antigen is a protein that tumor cells have and normal cells do not have,” explains Bryan.
According to the researcher from ICESP, the use of proteins present in a wide variety of tumors as a recipe for the immunizing agent allows the vaccine candidate to be used in the future to fight different types of cancer.
For Bryan, the development of a vaccine against cancer faces challenges such as the search for an adequate antigen that does not cause adverse effects in patients and that is capable of activating the immune response.
“The search for the right antigen to use in the vaccine is an issue. In the case of Covid-19, for example, it is very clear. With cancer, this is very complicated because we have thousands of different proteins and you never know which patient will express which of these proteins, which are different for each person”, he explains.
According to the University of Oxford, the next steps in the research include conducting a phase 1 and 2 clinical trial of the cancer vaccine in combination with immunotherapy. The start of the study, which should include the participation of 80 patients with lung cancer, is scheduled for the end of this year.