Advanced therapies are the result of the sum of biomedical knowledge, technological advances and data exploitation, and are granting an opportunity for life to patients so far with a short short-term prognosis due to failure of the rest of available treatments.
These therapies have come true the dream of a personalized medicine, giving a spectacular turn to approach some diseases for very selected cases of patients, to the point that there is a real biomedical revolution.
And is that new advanced therapies (specifically Car-T cells) have changed the panorama for patients with some hematological tumors, such as leukemias, lymphomas or myelomas, who did not respond to conventional treatments and those new treatments are
They have achieved positive results regarding the remission of the disease between 50 and 90% of the cases, according to Fermín Sánchez-Guijo, Vice President of the International Society of Cell Phone and Head of the Cell Therapy of the Hematology Service
University Hospital of Salamanca.
Also various gene therapy strategies are offering promising results in some congenital diseases.
More than 2,500 patients have already benefited in Europe with Car-T cell treatments, and in Spain, although there is no updated public data, applications have exceeded 500 patients.
The concept of advanced therapies does not refer, as initially could be interpreted, to the description of more or less modern or avant-garde therapeutic options, makes clear Sánchez-Guijo, but defines medications and health products obtained in a concrete manner, fulfilling
A requirements, and whose development has been regulated by the European Union through a directive that discriminates what it is and what is not advanced therapy.
As advanced therapies, medications based on the use of genes (gene therapy), cell therapy or tissue (tissue engineering) (tissue engineering) are described to prevent or treat various diseases, any combination of these alternatives, as it happens with the
CAR -T cells, in which gene and cellular therapy is used.
The use of cellular therapies in medicine is not a recent novelty.
An example is bone marrow transplant (currently called transplantation of hematopoietic progenitors), which offers a healing solution to many patients with diseases of blood through the replacement of their blood stem cells by those of a healthy donor.
However, when cells that are used for therapeutic purposes are subject to “substantial manipulation” cease to be regulated by transplant legislation and become defined as “advanced therapy drugs” and have to be regulated and marketed as the rest
From drugs, Sánchez-Guijo explains.
Another element that differentiates cell therapies from other therapeutic strategies is that they are “live medications”, that is, “the cells are multiplying and reacting differently depending on the signals they receive from the blood and tissues of the patient”,
Precise the expert.
This is one of the reasons why a narrow surveillance is key in the weeks after cell treatment to control the possible appearance of complications.
And that is why its development and administration are concentrated in specialized reference centers with very well trained human equipment to act on any complication.
In Spain, there are 15 public hospitals accredited by the Ministry of Health to administer Car-T therapies.
To understand CAR-T therapies, you must know how the immune system works before an external aggression.
Every day pounds a battle against the attacks from the outside.
It is an organized system to stay alive.
And it works very well … until it stops doing it.
Sometimes failure occurs by a factory defect, in others due to damage derived from our habits, and sometimes because external agents, such as tumor cells or viruses, also learn to develop strategies to deceive our system.
This defense system has a battalion of anti-sight cells, responsible for the rapid response, which is what macrophages and neutrophils are dedicated, among others, and more specialized elite forces, who develop a memory to act on special occasions,
how are T lymphocytes?
Car-T therapy works with these t lymphocytes that are extracted from the patient when they stop being effective in their defense function, and trained again in the laboratory so that they recover lost capacity.
For this, a receptor that is called a chimeric (because it combines a structure of an antibody with the receptor that activates the T lymphocyte) and multiply in the laboratory.
When injected back to the patient, they selectively recognize by these receptors to the tumor cell and eliminate it, indicates Fermín Sánchez-Guijo.
“We are getting some no-regard answers before, with very good results in 50 to 90% of the cases.”
Some of these patients maintain the response over time and others lose it, but another of the benefits of this therapy is that when the patient responds, a bone marrow transplant may arise, which is not indicated in case of resistant disease.
Eduardo López-Collazo, Scientific Director of the Hospital La Paz Research Institute, in Madrid, describes this progress as “incredible” and “one of the great achievements of the first decades of the 21st century,” and emphasizes that the challenge is now achieving
Similar results in the approach of solid tumors, in which the achievement of results goes slower, among other reasons because they have a greater access difficulty.
Immunotherapy, “with the use of antibodies blocking immunocheckpoints”, is also giving great joys to research, especially by the finding of strategies against elements that hinder communication between tumor cells and those of the immune system.
“It’s about raising a wall that prevents communication so that tumor cells can not get the message to those of the immune system to stop acting,” says López-Collazo.
This strategy is already a reality in the approach of lung tumors and melanoma «and we think that in the future you can reach almost all tumors.
For this, we must define the exact communication pathways that we want to inhibit, “explains this expert.
And this line is being applied in other diseases that have nothing to do with cancer, such as sepsis, in which an infection is generated and at the same time a disproportionate response of the immune system “because a bacterium achieves the cells of this system of
Defense stop working ».
In the case of gene therapy, it is about cure diseases by altering the patient’s genetic material, frequently through the introduction of a healthy copy of a defective gene in the patient’s cells that may be doing, for example, that
Do not produce an essential protein for life, such as insulin.
This strategy is beginning to bear fruit in the treatment of congenital diseases as certain immunodeficiencies, congenital blood disorders such as thalasemias and hemophilias and visual field diseases as retinal dystrophies.
One last advanced strategy is CRISPR technology, which uses guides and a protein to go to chosen areas of DNA and cut and paste, that is, edit genetic material.
It is being used to develop disease models that facilitate your study and to test new targets and drugs.
