There Is Hope For Childhood Leukemia: Gene Therapy
The most recent treatment against one of the most common types of cancer in the child population has not only managed to slow down the progression of the disease, but also managed to reverse it. Gene therapy represents a new form of hope for children suffering from childhood B-cell leukemia.
But to understand leukemia, we first need to know which cells are affected and how they originate. It all starts in the bone marrow, a white, spongy tissue located within the long bones such as the femur, pelvis and sternum.
In the bone marrow , there are a small number of stem cells that give rise to the different types of cells found in the blood: the lymphoid series (lymphocytes) and the myeloid series (red blood cells, platelets and some white blood cells). So how does B cell cancer start?
What is childhood leukemia?
All cancers arise when our bodies start producing cells at an uncontrolled rate, with the particularity that these abnormal cells do not die. Since our bodies are made up of cells, cancer can appear in any organ in the body.
In the case of childhood leukemia, cancer originates in the bone marrow, so the cells affected are blood cells, more specifically those that give rise to white blood cells or myeloid cells, myelocytes.
These cancer cells sometimes remain in the bone marrow, although they usually reach the bloodstream, thus spreading the disease and, in some cases, invading other parts of the body, such as lymph nodes, spleen, liver, and the central nervous system. .
Types of childhood leukemia
According to different characteristics, the American Cancer Society classifies childhood leukemia into the following subtypes: acute or fast-growing, chronic or slow-growing, myeloid cells or lymphoid cells.
- Acute lymphoid leukemia (ALL). It is the most frequent. It affects lymphoid cells, those that will form white blood cells. It is known as B-cell leukemia.
- Acute Myeloid Leukemia (AML). It originates in myeloid cells. It represents the majority of remnant leukemia cases.
- Chronic lymphoid leukemia (CLL). It is very uncommon in children. It affects white blood cells in the bone marrow.
- Chronic Myeloid Leukemia (CML). This variation originates in hematopoietic cells, those that give rise to red blood cells and platelets, in such a way that it invades the bloodstream. It is uncommon in children.
A new form of hope: gene therapy
Recently, the Hospital Clinic de Barcelona treated several children with B-cell ALL who did not respond to conventional treatment.
A new gene therapy that is still in the experimental phase in humans was then applied: tisagenlecleucel. This treatment was approved by the FDA in 2012 and is distributed by the pharmaceutical company Novartis. But what exactly is gene therapy?
gene therapy
Gene therapy is a treatment tailored to each patient. In this therapy, specific genes are introduced into certain cells of the patient in order to fight the disease. In this way, it is possible to avoid transplant rejection and increase the effectiveness of treatment, designing specific targets to attack cancer.
Treatment planning for childhood leukemia
The process takes place in several steps and takes about 22 days to complete.
- First, the patient’s blood cells are extracted and T lymphocytes are isolated.
- Then, in the laboratory, they are genetically manipulated. A DNA sequence is included to produce a protein called CAR ( Chimeric Antigen Receptor ) .
- CAR is responsible for recognizing another protein located on the surface of cancer cells, CD19.
- The patient’s modified T-Lymphocytes (TL) are cultured in the laboratory until billions of them are obtained.
- In a final phase, the modified TL is inoculated into the patient as an intravenous infusion.
How does the T-CAR / CD19 binomial work?
Imagine the cell as a sphere on the surface of which sprout some branch-like structures, each with a characteristic morphology. These branches will be responsible for the cell’s relationship with the environment and with other cells.
In the specific case in question, the patient’s modified TLs express on their surface a very specific ‘twig’, the CAR, which recognizes another specific ‘twig’ on the BL surface, the CD19. Once the T lymphocyte recognizes the cancerous B cell, it can proceed with its elimination.
However, in the words of Dr. Francis Collins, director of the NIH:
Successes and failures of immunotherapy in childhood leukemia
In the results observed after 3 months of application of the treatment, according to the National Cancer Institute (NIH), 80% of patients who did not respond satisfactorily to conventional chemotherapy had a clear remission of the disease.
However, we must be cautious in the face of this successful immunotherapy in view of the side effects observed and that must be taken into account. Dr.Collins presented a report in which the following points should be highlighted:
- The CD19 protein is present on B lymphocytes, such that LT-CDR does not distinguish between healthy and cancerous cells, and the patient must be treated for immunosuppression.
- Appearance of Cytosine Release Syndrome, which is remedied after the application of timely medication.
- Presence of neurological side effects, such as confusion and seizures, which appear to be reversed without being treated.
Undoubtedly, this innovative treatment represents new hope for the families of these children who were without other possible paths to follow.
Although it has not yet been perfected and is in the experimental phase, its good results have facilitated the approval of immunotherapy for the treatment of other types of cancer, such as HPV or lymphomas.
