Designer T-Cells Aid in Treatment of Leukemia
The only thing worse than hearing the word cancer is in reference to a child. A mere 3 months after delivering a seemingly healthy baby girl that they named, Layla, Lisa and Ashleigh Richards got the worst imaginable news. They were told their infant daughter was suffering from acute lymphoblastic leukemia (ALL), a type of cancer in which the bone marrow makes too many immature lymphocytes, a type of white blood cell (WBC) involved in moderating the immune system. ALL is the most common type of cancer in children and in aggressive forms has about a 1 in 4 survival rate.
There are two main types of lymphocytes: B cells and T cells. The B cells produce antibodies that are used to attack invading bacteria, viruses, and toxins. The T cells destroy the body's own cells that have themselves been taken over by viruses or become cancerous. ALL usually goes undetected until the child becomes symptomatic. Often it is mistaken for an infection unless accompanied by unusual bleeding, so routine blood tests should be a standard diagnostic tool.
Normal blood cells have a life cycle of about 90 days. However cancerous cells do not undergo cell death or apoptosis and in the case of ALL the bone marrow does not behave normally and keeps producing WBCs which eventually crowd out other types of blood cells. Red blood cells are responsible for carrying oxygen (O2) to the cells and platelets are responsible for forming clots which prevent bleeding. When either type of cell is extremely low it is considered a medical emergency.
Pediatric ALL is thought to be caused by either inherited or acquired DNA mutations which may develop in utero. In rare cases, acquired mutations can result from exposure to radiation or cancer-causing chemicals, but most cases of ALL are idiopathic, having no known cause.
ALL is diagnosed via a complete blood count. In baby Layla’s case, she presented to the doctor with anorexia, frequent bouts of crying and shortness of breath secondary to a rapid heart rate. Initially infection was suspected but her blood test was alarming enough that she was immediately transported by ambulance to Great Ormond Street Hospital (GOSH) in London, UK and placed in the neonatal intensive care unit (NICU). Her treatment included several rounds of chemotherapy followed by bone marrow transplant.
How The Treatment Worked
Initially the treatment was thought to be successful but, some of the leukemic cells survived the treatment. Seven weeks later doctors told her parents the treatment had failed and they had run out of options. They suggested palliative care but the Richards refused to give up.
Specialists in genetic engineering who were conducting pre-clinical phase research at GOSH and University College London’s (UCL) Institute of Child Health heard about Layla’s case and offered an innovative new off label therapy that was still in an experimental stage. While testing had only been performed on mice and there were potential risks the researchers felt any danger paled in light of the child’s current prognosis. They approached the ethics committee for permission to use the technology for compassionate use and their request was granted.
The technology uses genetic modification on T-cells harvested from healthy donors. A patented molecular tool called (TALEN®) is used to cut specific genes in order to make the T-cells immune to chemotherapy drugs and reprograms the T-cells to target and fight against leukemia cells. Only a tiny amount - 1 millimeter - of genetically modified T-cells is injected into the patient.
Once the procedure was over, Layla had to spend months in isolation in order to avoid getting an infection due to her compromised immune system. After she began showing signs the treatment had worked, a rash that indicated an immune response, she underwent another bone marrow transplant. Today Layla Richards is cancer free and her parents are extremely happy.
"As this was the first time that the treatment had been used, we didn’t know if or when it would work and so we were over the moon when it did” said Professor Paul Veys, Director of bone marrow transplant at GOSH and the patient’s lead clinician. “Her leukemia was so aggressive that such a response is almost a miracle."
While Layla’s results are extremely promising more research and phase 1 and 2 clinical trials will have to be performed before researchers can apply for permission to the Medicines and Healthcare products Regulatory Agency (MHRA) for routine use in the UK. Layla will receive monthly blood tests and follow up care to determine if she remains cancer free, but her case will be one for the history books and has definitely opened up the possible treatments for this deadly disease.