Last August, the clinical trial process for the Cuban-patented drug Itolizumab began in China. The research will be carried out by a joint venture of both countries named Biotech Pharmaceuticals Limited (BPL). According to its directors, it will also begin studies in 2025 to validate Cimavax, the Cuban lung cancer vaccine to which we dedicated an article in this column.
Itolizumab will be tested on patients with dermatomyositis and will also be used for graft-versus-host treatment. Dermatomyositis is a disease that affects the muscles and skin and is common in children and people suffering from different types of cancer. Its causes, according to an article from the United States Medical Library, are not fully known, but it is suspected that it has an autoimmune origin and is related to the presence of a viral infection. A hypothesis that has gained strength in recent times is its relationship with the Epstein-Barr Virus, which causes the “kissing disease.” Dermatomyositis has manifested in some cases after infection by this agent.
Graft versus host or recipient, on the other hand, is an inflammatory disease that appears after a transplant of stem cells, bone marrow or organs in the body of the recipient patient; it causes rejection of the transplanted organ or tissue and increases mortality, according to the National Cancer Institute of the United States. So far, this disease has as its only treatment the use of high doses of steroids, which have multiple adverse effects.
Itolizumab became known within the medical community in Cuba in the dark days of the COVID-19 pandemic. At that time, it was one of the tools available for the treatment of severe forms of this disease.
But, in essence, what is Itolizumab? What is its mechanism of action? What prospects does this novel drug have?
Immunotherapy, a necessary explanation
One of the fields that generates the most scientific results in contemporary medicine is immunotherapy.
This revolutionary branch of medicine seeks to prevent and cure diseases through the use of different types of drugs that act on the immune system. As you may remember, the immune or defense system is responsible for protecting the body from enemies, both internal and external. Among them we have viruses, bacteria and also neoplastic cells.
A classic example of immunotherapy are vaccines. Since the beginning of the 19th century, these therapeutic tools have prevented diseases and saved millions of lives, by preventing certain germs from infecting the body or, if they do, generating a mild form of the disease.
This is a fascinating field that has produced extraordinary results over the past 50 years, some of which have been awarded the Nobel Prize in Medicine, such as monoclonal antibodies. These were discovered in the 1970s by researchers at the University of Cambridge, César Milstein and Georges Köhler.
To better understand what follows, we must briefly explain what antibodies are. They are proteins produced by the body with the ability to identify specific targets, called antigens, which are attacked by the immune or defense system.
They are a kind of highly specialized scout that warns infantry about the presence of an enemy, such as a virus, bacteria or cancer cell. Sometimes something goes wrong and the defense system itself attacks the body, in a spontaneous response that could be called “friendly fire.”
For nearly 50 years, scientists have found a way to produce artificial antibodies in laboratories. These are monoclonal antibodies, and there are several types, depending on their therapeutic use. Itolizumab is one of them.
Each antibody, whether natural or artificial, is capable of identifying a specific antigen. In the case of Itolizumab, this is a protein called CD6. It is found on the surface of a group of defensive cells known as T lymphocytes.
CD6, “igniter” of immune system
At the time you read these lines, your immune system is facing one or more attacks. Routinely, a formidable army of cells with highly specialized functions defend us. One of the mechanisms by which this happens is the so-called inflammatory cascade.
I will try to explain this complex phenomenon in the simplest way possible. When an antibody detects an antigen, it summons a group of cells, which begin to multiply and produce substances known as inflammatory mediators. Their function is essentially to mobilize new cell groups with specific functions to control the threat.
In parallel, another group of substances and cells ensure that the damage does not outweigh the benefit. This must work like a fine-tuned clockwork mechanism. Unfortunately, this does not always happen. In some diseases, the immune system attacks structures of the body itself, as is the case with psoriasis and rheumatoid arthritis, two diseases classified as autoimmune. Other times, the very nature of the attack is such that the immune system itself can cause the death of the patient, as we saw happen during the COVID-19 pandemic, and with other deadly germs.
Finally, in some special occasions it is necessary to reduce the capacity of the immune system, as occurs in the cases of bone marrow or kidney transplants, to prevent the body from rejecting the “foreign body.”
In these circumstances, having an “igniter” of the immune system that, without completely leaving the body unprotected, modulates the inflammatory response, is quite useful. Such is the case of the CD6 protein.
Since the late 1990s, this molecule began to generate interest among the scientific community due to its properties as an activator of the immune system.
A decade later, several monoclonal antibodies had already been created whose function was to identify and inactivate the CD6 protein; among them was Itolizumab, which was supposed to, in very simple words, “turn off” some functions of the immune system.
This opened up enormous possibilities for the treatment of autoimmune diseases and other pathologies in which control of the inflammatory response was vital. The first results soon began to appear.
Itolizumab and psoriasis
Itolizumab is a monoclonal antibody developed by Cuban researchers. The first studies on its practical use were published in 2011, when it was included, under the name Th1, by which it was known at that time, as one of the 25 monoclonal antibodies of interest to the scientific community.
From 2010 to the present, dozens of investigations have been published that confirm the veracity of the initial hypothesis, that is: Itolizumab is useful in the treatment of autoimmune diseases, such as psoriasis. It also has an adequate safety profile, that is, it generates few adverse reactions and of low severity.
According to an article published on the website of the National Institutes of Health of the United States, psoriasis is a chronic, autoimmune disease. There are different forms of presentation of this pathology. The most common form is lesions in the form of raised plaques that are located mainly on the scalp, trunk and extremities, with a preference for certain areas such as the knees and elbows.
A Cuban study showed the safety and efficacy of the use of Itolizumab in patients with moderate and severe psoriasis. In the same sense, a case report of a patient who, after 5 years of having received treatment with Itolizumab, remained in remission of her psoriasis is interesting. This means that she did not present symptoms of her disease, or that it was “silenced” by the drug.
A particularity of Itolizumab is that it was developed jointly by Biocubafarma, the Cuban biotechnology conglomerate, and Biocon, an industry in the same sector in India. Hence, studies on the drug have been developed in parallel in both countries.
Itolizumab and COVID-19
The arrival of the pandemic created the need to look for treatment options. Both in Cuba and India, studies were carried out that had as a common denominator the use of Itolizumab in patients with moderate and severe forms of the disease.
The cause of death of most COVID-19 patients was not the direct action of the virus, but the damage caused to the body by the cytokine storm. When we talked about the inflammatory cascade before, we were referring to this phenomenon. It is the uncontrolled action of the immune system induced by the virus. In this context, it will be understood that a modulator of the defensive system such as Itolizumab had all the traces of being useful.
A study conducted in India showed a reduction in mortality and oxygen needs in patients with moderate and severe forms of COVID-19 who were being administered Itolizumab.
Meanwhile, a Cuban multicenter study1 that included a dozen hospitals across the country showed that Itolizumab reduced oxygen needs and comparatively reduced mortality in patients with moderate and severe COVID-19 when its use was appropriate.
Once the pandemic was over, Itolizumab continued to be used in Cuban intensive care units for the treatment of patients with specific forms of acute respiratory failure. My experience in this context, although anecdotal and not investigative, confirms the usefulness of the drug in this type of patient.
A path that is expanding
Beyond the proven efficacy of Itolizumab in patients with psoriasis and COVID-19 inside and outside Cuba, the path of this monoclonal antibody is expanding. An example of this is the start of the clinical trials that we referred to at the beginning of the article.
In addition to the clinical trial with Cuban participation that is being carried out in China, the U.S. company Equilium is carrying out a similar investigation. This biotechnology company acquired the rights to use Itolizumab from Biocon. The study is directed towards graft-versus-host disease, which we referred to.
Additionally, an article published on the Lupus Foundation of America website tells us about the encouraging results of the use of Itolizumab in patients with lupus nephritis, that is, the kidney damage caused by lupus in patients with this disease.
It is good to remember that lupus is another of those autoimmune diseases that cause a notable reduction in the quality and life expectancy of those who suffer from it. Kidney damage is the cause of death in some of these patients. The study in question shows a reduction in several of the most important indicators of this disease.
As can be seen, the path of Itolizumab is expanding and its possible uses for the treatment of various diseases are diversifying. It is undoubtedly gratifying to see how a drug produced in Cuba is making its way into the world and that its possibilities of saving thousands of lives are increasing.
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Note:
1 Multicenter studies are being developed simultaneously in several health institutions. Their objective is to cover a larger sample in a shorter period of time, which gives robustness and greater reliability to the results.
Author
Carlos Alberto González
thank you for giving such simple details of this drug it is so easy to understand the process you have discribed ,and the potental benifits to the layman …. Bert