The journey of a five year old child is a glittering example of bravery in the struggle against leukemia. Emily “Emma” Whitehead was the first child in the world to receive T-cell therapy (GMTs).
“Emily was diagnosed with acute lymphoblastic leukemia (ALL) at age five in May 2010 and relapsed twice. After the second relapse, the Whiteheads were told they were out of options to treat her cancer. Not willing to give up, the Whiteheads pursued a radical new treatment called T-cell therapy at Children’s Hospital of Philadelphia (CHOP).”
In April of 2012, Emily was enrolled in Phase 1 of an experimental clinical trial where her T-cells were genetically reprogrammed to recognize and attack cancer cells.
Emily had a stormy post-treatment course when the T-cells were put back into her body. She was in intensive care unit in a coma and on a ventilator for several weeks. At one point the doctors told the parents that Emily had “only a 1 in 1000 chance to survive the night.”
Clinical investigator, Dr. Carl H. June talked with Emily’s doctors at CHOP. As a last resort, they decided to drip into Emily’s vein a rheumatoid arthritis drug (a Hail Mary pass) to counteract the horrible side effects of the treatment.
Well, their prayers were answered. She made it through the night and 14 days later Emily awakened on her 7th birthday. Remarkably, several weeks after her 7th birthday, laboratory tests indicated Emily was cancer free. And T-cells continued to circulate throughout her body.
Emily is a warrior. She is now more than 5 years cancer free, goes to school, plays soccer and loves to read.
On August 31, 2017, the Food and Drug Administration approved T-cell therapy for certain forms of leukemia. Scientists and oncologists herald this event as a new day for immunology and the treatment of cancer.
The immune system protects the body against disease, cancer and foreign invaders. It’s a sophisticated department of defense that works 24/7 every day of the year. The system recognizes, neutralizes kills and removes unwanted characters from our body. Some of those characters include bacteria, viruses, fungi and, of course, cancer.
T-cells, a type of white blood cells, are part of the immune system and one important mission is to defend the body against the relentless attack of cancer cells. All too often the immune system loses the war against cancer, because T-cells don’t recognize cancer as a foreign body or they don’t have enough T-cells to fight cancer or the cells are not functioning properly.
The medical breakthrough is the use of the patient’s own T-cells which have been re-programmed to treat cancer. What follows are highlights of CAR T-cell technology and how doctors use it to help cancer patients.
CAR T--Cell Therapy uses genetically modified T-cells (GMTs) from your own immune system to seek and destroy cancer cells. It’s a stepwise process that presently takes anywhere from10 days to several weeks for scientists to re-program your unique T-cells.
- Blood is drawn from your vein and hooked up to a machine to remove white blood cells including T-cells. The other components of the blood are returned to your body. This process is called apheresis or leukaphoresis.
- The T-cells are cryopreserved—preserved by cooling them below the freezing point of water
- The cells are shipped to a bio-engineering laboratory. They are thawed and made ready for scientists to create your, one of a kind, CAR T-cells.
- Scientists mix the collected T-cells with disabled viruses. The viruses carry genetic instructions to the T-cells directing them to multiply and form radar receptors that will seek, target and kill cancer cells.
These protein receptors are called CAR—Chimeric Antigen Receptors The CAR receptors are “living drugs” that do not exist naturally. - Millions of newly created CAR T-cells are once again cryopreserved, shipped back to the original hospital or clinic, thawed and put back into the patient’s vein.
CAR T-cells travel throughout the bloodstream looking to bind with proteins (antigen CD19) on the surface of cancer cells. Once they dock with CD19, they release toxic materials that kill the cancer cells.
The dead cancer cells can weigh more than three pounds, which can overwhelm a child’s body and precipitate a cytokine storm (see below) as in Emily’s case, with horrible side effects. - Next, you’ll be monitored in the hospital for side effects which can be life threatening--temperature of 105, drop in blood pressure, respiratory difficulty…
- Continued follow-up and treatment after being discharged from the hospital.
T-cell therapy is in the early stages of development with hundreds of clinical trials now underway. The future is promising but not certain. As with any medical innovation, there is initial enthusiasm, followed by objective clinical trials and sober conclusions as to the risks, costs and long term benefits of the new treatment.
Unquestionably, this is a new paradigm and a potential game-changer in the treatment of cancer patients. Much gratitude and thanks must be given to the many valiant patients such as Emily, their families and doctors for “changing the odds against cancer.”
References
1--Emily Whitehead Foundation
NIH National Cancer Institute’ Immunology: Using the Immune System to Treat Cancer; Sept. 8, 2017
NIH CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers; Dec. 14, 2017
Renier J. Brentjens, MD, PhD CAR T Cells in Acute Lymphoblastic Leukemia January-February 2015, the Hematologist
Anticaglia, Joseph R; A Snapshot of the Immune System Our Bodies’ Department of Defense; HC Smart, 2017
Anticaglia, Joseph R; “The Boy in the Bubble” Recurrent Infections in Children When Should I Worry? HC Smart, 2017
Scheuerman RH, Racila E; CD19 Antigen; Leukemia and Lymphoma; August, 1995
Glossary
CARs (Chimeric Antigen Receptors) are proteins that allow T-cells to recognize an antigen on targeted tumor cells. The re-programmed T-cells with the receptors are “living drugs that do not exist naturally.”
Cytokine storm is an inflammatory response sizzling out of control--an immune system gone haywire.
Tocilizumab is the arthritis drug given to Emily
Carl Hl June, MD is an early, clinical investigator re CARs T-cell therapy
This is intended solely as a learning experience. Please consult your physician for diagnostic and treatment options.