The vaccines they are one of the most necessary and revolutionary developments of humanity. One of them made it possible to eradicate smallpox, others have reduced deaths from yellow fever, measles and meningitis, And now it is they who allow almost everyone to return to a relatively “normal” life after the most difficult period of the pandemic caused by the SARS-CoV-2 coronavirus. The basic working principle of vaccines, whatever it is, is extremely simple: encourage the body to identify and fight an agent foreign to the body.
Based on this concept, researchers in the field of cancer have wondered for decades what would be the effect of having an immunizing substance against the disease, taking into account that tumors are abnormal conglomerates of cells that grow between tissues, thus configuring themselves as something alien to the nature of the organs. It has not been easy to find the answer, but last month the Cleveland Clinic, in the U.S, shows that scientific researchers are on the right and promising path.
Considered one of the best in the world, the American Center for Treatment and Health Research announced that it has started a clinical trial to test the efficacy and safety of a vaccine for prevent and treat the most aggressive type of breast cancer. If it works, it will be the first immunizing agent capable of directly preventing the appearance of a tumor. Currently, there are indirect protection options, such as HPV vaccines (Human Papillomavirus) and hepatitis B.
The first acts on some types of virus responsible for tumors, such as the one that causes cervical cancer. The second protects against infections by the hepatitis B virus, a disease that promotes chronic inflammation of the liver, making liver cells vulnerable to the uncontrolled proliferation characteristic of cancer.
The study
Developed in conjunction with the company Anixa Biosciences, the immunizing agent will be tested against triple negative breast tumor. Although it affects up to 15 percent of women with the disease, triple negative is the most difficult form of breast cancer to treat. Diseased cells do not have receptors for the hormones estrogen and progesterone and do not produce the HER2 protein (hence the triple negative name). HER2 is a gene that makes a protein that is found on the surface of all breast cells.
Due to this triple negative quality, this type of cancer does not respond to hormonal therapy and the drug designed to act on HER2 is not helpful. If the disease is diagnosed late, the prognosis is poor.
“But we are hopeful that our work will be the beginning of more advanced research demonstrating the efficacy of the vaccine in stopping the breast tumor for which we have fewer available treatments,” says hematologist Thomas Budd of the Taussig Cancer Institute, division of the clinic where the study will be conducted.
In this first phase of the clinical trial, 18 to 24 patients who were diagnosed with cancer at an early stage in the last three years will participate in the study, although they do not have the tumor, they do have a high risk of recurrence. Until September 2022, when this branch of research will end, each of the volunteers will receive three doses of the vaccine, applied two weeks apart.
At this stage, the goal is to examine the immune response triggered by the vaccine and side effects. That is, to evaluate the performance of the immunizing agent from a therapeutic point of view. The analysis of its preventive power will be carried out in a later step, with the recruitment of women without cancer, but with a high risk of developing it and who underwent voluntary removal of both breasts as a way to reduce the probability of tumor appearance.
Background
The basis for testing in humans comes from previously positive results obtained over more than a decade of research in laboratory cells first and guinea pigs later. The main study was published in 2010 in the scientific journal Nature. In the article, the scientists showed that the vaccine prevented the appearance or stopped the growth of the tumor in animals.
Vaccines, as we know them, are designed to provoke a constant defense reaction in the body against an infectious agent. Conventionally, this is done by presenting the intended virus or bacteria to the body in inactive or weakened forms, but sufficient to alert the immune system to the invasion and encourage it to contain the enemy.
About a year ago, the world discovered another technology, messenger RNA (mRNA), used in the production of Covid-19 vaccines by companies. Pfizer-BioNTech and Moderna. In this case, the genetic material created in the laboratory is used to teach human cells to make a protein originally developed by the virus or bacteria in question. Thus, the body also learns to recognize the molecule and the virus as threats, accordingly. If you are infected by the microorganism, you will fight it.
When it comes to cancer vaccines, the issue is more complex. Although the rationale is the same, the targets that will be activated to alert the defense army are not easily identifiable. Since cancer arises from a person’s own cells, it is difficult for the immune system to see the proteins produced. That is why it is very complex to find the specific substance, produced by each tumor, capable of awakening the immune system. The vaccine developed at the Cleveland Clinic overcame the hurdle by targeting a molecule present in 70 percent of tumor cells in women with triple-negative breast cancer.
In addition, the establishment and growth of the tumor indicates that the immune system is not that strong and that the dose to strengthen it may be as intense as it is unfeasible. These obstacles explain the small number of vaccines available. The few options are limited to serious tumors, such as Provenge, for patients with prostate cancer that have not responded to previous treatments, and T-VEC, approved to treat melanoma, the most aggressive type of advanced skin cancer.
However, the increased knowledge of the characteristics of tumors that exists today prompted the investigation. In the registry of ongoing clinical studies in the United States, there are dozens of vaccines that involve tumors of the lung, liver, and intestine, among others.
One of the most interesting takes place at Memorial Sloan Kettering, in New York, where the effectiveness of an immunizing agent made with mRNA technology against the pancreatic tumor. Doctors found the right target by investigating why some patients survived longer than average. In them was a molecule so different from the others that it served as a decoy for the defense system.
The goal of the vaccine is to teach tumor cells from other patients to make molecules like this one. In Texas, the Center for Nanomedicine develops nanovaccines that serve as the basis for immunization against leukemia and lymphoma. The new path is finally open.
