The New Hope Of Childhood Leukemia: Gene Therapy – Parenthood

The most recent treatments for one of the most common cancers in childhood have not only succeeded in slowing the progression of the disease, but have even helped to reverse the trend. Gene therapy is a new hope for these children with B-cell leukemia.

But to understand leukemia, we first need to know its origin as well as the cells it affects. It all starts in the bone marrow, a white spongy tissue located inside long bones such as the femur, hip, and breastbone.

In the bone marrow, there are a small number of stem cells that produce 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). Let’s dive into the heart of the matter, how does B cell cancer occur?

What is childhood leukemia?

Cancer occurs when our body begins to produce cells at an uncontrolled rate. The subtlety is that these abnormal cells do not die. Because our body is made up of cells, cancer can appear in any organ in the body.

In childhood leukemia, the cancer takes root in the bone marrow. The affected cells are therefore blood cells, more particularly those which give rise to white blood cells or myeloid cells, myelocytes.

These cancer cells sometimes remain in the bone marrow although sometimes they reach the bloodstream, spreading the disease. In some cases, they invade other parts of the body. For example, cancer cells can reach the lymph nodes, spleen, liver, and central nervous system. However, there is hope for childhood leukemia: gene therapy.

The different types of childhood leukemia

According to different characteristics, the American Cancer Society classifies childhood leukemia according to the following subtypes: acute or rapidly growing cells, chronic or slow growing cells, myeloid cells or lymphoid cells.

• Acute lymphocytic leukemia (ALL). It’s the most frequent case. It affects lymphocyte cells, the ones that will form white blood cells. It is better known as B cell leukemia.
• Acute myeloid leukemia (AML). It comes from myeloid cells. It represents the majority of leukemia cases.

• Chronic lymphocytic leukemia (CLL). It is a very rare type of leukemia in children. It affects the white blood cells in the bone marrow.
• Chronic myelogenous leukemia (CML). This variant has its origin in hematopoietic cells, those which give rise to red blood cells and platelets, thus invading the bloodstream. It is also very rare to see it in children.

Hope for families: gene therapy

Recently, the Hospital Clinic in Barcelona treated several children with B-cell ALL who have not responded well to conventional treatment. They were administered a new gene therapy still in the experimental phase in humans: tisagenlecleucel. This treatment was approved by the FDA in 2012. The pharmaceutical company Novartis is responsible for producing it. But what is gene therapy?

Gene therapy

Gene therapy is a treatment adapted to each patient. During this treatment, specific genes are introduced  into certain cells of the patient to fight against the disease. In this way, it is possible to maximize the chances of avoiding transplant rejection and increase the effectiveness of treatment by designing specific targets to fight cancer.

The concept of treatment for childhood leukemia by gene therapy

The process takes place in several stages and takes about 22 days.

• First, the patient’s blood cells are taken and isolated   T lymphocytes.
• Later, in the laboratory, they will be subjected to a genetic modification. Indeed, we will include a DNA sequence to produce a protein called CAR (Chimeric Antigen Receptor).
• RCA will then recognize another protein located on the surface of cancer cells, CD19.
• The patient’s T cells (LTs) that have been altered are grown in the lab for billions.

• In the final phase, the modified LTs are inoculated into the patient as an infusorium intravenously.

How does the T-CAR / CD19 pair work?

Imagine the cell as a sphere, the surface of which has certain branch-like structures, each with a characteristic morphology. These branches are responsible for the cell’s relationship with its environment and with other cells.

In the specific case, the patient’s modified LT surface expresses a very specific “branch”, CAR, which specifically recognizes another “branch” on the surface of the LB, CD19. Now that the T lymphocyte has recognized the B cell, it can eliminate it.

However, let’s keep in mind the quote from Dr. Francis Collins, director of the NIH:

The successes and failures of immunotherapy in childhood leukemia

According to the results observed after 3 months of application of the treatment, 80% of patients who have not responded satisfactorily to conventional chemotherapy are in clear remission of the disease, according to the National Cancer Institute (NIH).

However, one should be careful about this success of immunotherapy because of the observed side effects. Indeed, they must be taken seriously into account. Dr Collins has also submitted a report in which the following points should be emphasized:

• Because the CD19 protein is present in B lymphocytes, LT-CDR does not distinguish between cancer and healthy cells. This is why the patient should be treated for immunosuppression.
• The emergence of cytosine release syndrome, which subsides after timely application of drugs.
• The presence of neurological side effects, such as confusion and seizures, which seem to reduce without treatment.

Of course, this innovative treatment brings new hope to the families of these children who have this particular form of cancer. Although the treatment is not yet perfect and is still in the experimental phase, the good results have facilitated the approval of immunotherapy to treat other cancers, such as HPV or lymphomas.