The graduate of the Faculty of Health Diana Bonilla works in the team of James P. Allison, winner of the Nobel Prize in Medicine. She is one of the researchers involved in immunotherapy against cancer, the new medical revolution.
One in three people in the world, sooner or later, will develop cancer. Immunotherapy, which stimulates the patient's immune system to defeat tumor cells, has become the great medical hope. Diana Bonilla works with James P. Allison, winner of the Nobel Prize in Medicine, to perfect this treatment.
In 1891 the doctor William B. Coley, son of an old family established in Connecticut, graduated from Yale University and Harvard University, cured a patient with intractable cancer. At a time when there were no therapies for that disease, except for vague surgeries, Coley injected his patient with a bacterium, a streptococcus, in the hope that his immune system would not only attack the invading organism but also the tumor.
Coley had taken the idea of old medical reports. For example, in 1725 the doctor Diedier noticed that patients with syphilis developed fewer malignant tumors. James Paget mentioned in his notes that infections caused tumor regressions in some patients. In 1867, the German doctor Busch reported the disappearance of a tumor in one of his patients who contracted erysipelas. Coley discovered at least 47 cases in the medical literature that encouraged him to follow that path.
But luck did not treat Coley well. Although today he is considered the father of immunotherapy against cancer, the little regularity in his results, including deaths from the infection, created suspicions among his colleagues and ended up accused of being a chatterbox. A name that was unfair considering that a century later, thanks to the work of his heirs - among them James P. Allison and Tasuku Honjo, who have just been recognized with the Nobel Prize in Medicine -, hundreds of patients in the world have begun to be cured of some tumors considered intractable until now. Among them the brutal melanoma.
The Colombian Diana Bonilla is one of the researchers involved in this new medical revolution. She is part of one of the two teams that Allison runs at the MD Anderson hospital cancer center, associated with the University of Texas and ranked number one in cancer care in the United States. One of the groups is focused on basic science and creating new therapies. The other, to which Diana belongs -in which doctors of various disciplines are involved-, applies the therapies, evaluates them, tries to decipher what is the best strategy and why it works in some and not in others.
"Dr. Allison has been nominated several times for the Nobel Prize. His scientific career is impressive. We had the fortune to see the application of the findings he made for several decades" Bonilla recounts from Uruguay, where she found out about the Nobel announcement while participating in a meeting about these therapies.
In the 1980s, Allison, like many other researchers, devoted her efforts to describe the basic mechanisms used by the immune system to defend the human body from "strange" elements without harming the "owns". While many of them concentrated on using that knowledge to fight autoimmune diseases, such as arthritis or lupus, Allison took a different path. Unlike Coley, he noted that it was not necessary to attack cancer by activating the immune system with an infection. It was enough to learn to turn the system on or off by manipulating the T lymphocytes, cells that fulfill the role of soldiers of the immune response.
Allison concentrated his attention on one of the switches in the system: the CTLA-4 protein, on the surface of those soldiers of the immune system. He discovered that the CTLA-4 works like a brake. “What would happen if I remove that brake?” Allison decided to try mice and in a laboratory at the University of California, Berkeley, in 1994, applied an antibody, a bullet, that blocked that molecule.
"The result was spectacular", recalled this week in a summary of their work the managers of the Karolinska Institute, in Sweden, responsible for naming the winners of the Nobel Prize in Medicine. The next step was to demonstrate it in humans. But given the lack of interest of the pharmaceutical industry for a treatment based on the elimination of the brakes of immune responses, Allison managed on her own and partnered with Alan Korman of Medarex, a small biotechnology company. They used transgenic mice to produce human monoclonal antibodies. They called them anti-CTLA-4 IgG1 or MDX-010. Bullets that blocked the protein. It was barely a year before the turn of the century. It was then when the company Bristol-Myers Squibb became interested in the matter, bought Medarex and launched the scientific machinery to perfect the therapy.
In 2001, a patient with metastatic melanoma, Sharon, received one of the first doses of MDX-010, whose name had already mutated to Ipilimumab. After 18 years, Sharon is still alive, so she found out that the researcher who developed the treatment won the Nobel Prize in 2018. Something similar happened with the other Nobel winner: Tasuku Honjo, who discovered another of the immune system's brakes. PD-1 molecule.
Diana met Sharon. "At that time, people like Sharon with metastatic melanoma had no other alternative. They were death sentences," she reflects, "radiotherapy and chemotherapy are very aggressive treatments. With immunotherapy, the patient's own lymphocytes learn to kill the tumor and also keep memory in case it reappears.”
One problem is that for the treatment of melanoma, Ipilimumab works in about 30% of patients and when nivolumab (which acts against the PD1 protein of lymphocytes) is added, the rate of remission of the tumor rises to 60% . With chemotherapy the figure was less than 20%. The questions that Diana and her colleagues now raise are: why does not it work at all? What signs exist in patients' cells to know if they are going to respond to treatment? How do these signals correlate with what doctors see in the office? How to improve the effectiveness?
The other task is to try immunotherapy in other types of cancer. Technically they are called immunological checkpoint therapies. In fact, dozens of clinical trials are already underway in the world to evaluate the effectiveness of lung, pancreas and prostate cancer, among others.
"Given the perhaps unprecedented research activities in the immunological checkpoint field, there are likely to be important advances regarding this therapy at all levels. This shows how influential Allison and Honjo's discoveries have been. Their findings have conferred great benefit to humanity; add a new pillar to existing cancer treatments," said the Karolinska Institute.
It is a race against time and a battle against the high costs of medicines. According to the World Health Organization, more than 18 million people are diagnosed with cancer each year. With an aging population that is more exposed to environmental risks, those numbers are only expected to continue increasing. And unfortunately, these biological treatments surpass US $ 100,000 (COP$ 300 million), creating a huge barrier of access for patients in developing countries.
Diana says that it has been a great pride to work in Allison's group: "I believe that her work is an example that all those basic research efforts are worthwhile, because that is where the treatment to cure thousands of patients was derived."
Nobel winner James P. Allison with Diana Bonilla