Over the past 40 years, carefully combining chemotherapy, radiation therapy and surgery has brought the overall cure rate for childhood cancer to nearly 80 percent. However, for many cancers, these conventional therapies have reached a plateau. At the same time, we have experienced an explosion of knowledge in understanding how cancer cells grow and function, and how our own immune system works to fight cancer.
From organs to cells to genes and back again
The first success in repairing damaged tissue by transplanting tissue from healthy donors was 100 years ago – first with heart valves and pieces of bone, then, a few decades later with whole organs like hearts and kidneys.
By the 1950s we were able to be more selective in determining which cells we needed to transfer, and by the 1980s we had the first success with delivering individual genes. Now we are using that knowledge to:
- Put several genes together for improved function
- Add new function to cells using genetic engineering
- Put multiple cell types together to reconstruct entire organs instead of just repairing them
Along the way, we learned that differences between these therapies are not black and white. Cells transferred to a patient can help regenerate damaged tissues and healthy cells can correct disease by introducing new healthy genes.
Attacking Cancer with Bone Marrow Transplants (BMT)
A major reason for the success of BMT in treating leukemias is the function of the new immune system that comes along with it. The patient’s own immune system is cleared out by intense chemotherapy, and the donor’s immune cells are then transplanted along with the bone marrow stem cells. The new immune system from the donor then identifies, attacks and destroys remaining cancer cells in what is called the “graft-versus-tumor” effect.
Attacking Cancer with T Cells and NK Cells (Cellular Immunotherapy)
T cells and NK cells are important parts of the immune system transferred from the donor in a BMT.
T cells are like assassins – they are taught to “seek and destroy” specific kinds of dangerous cells. Sometimes the cancer learns how to disguise itself and hide from the T cells, escaping recognition.
NK cells are more like border patrol agents. They monitor the cells throughout the body looking for cells that look dangerous or don’t have a valid passport. More specifically, NK cells study the proteins on cells and compare the good versus bad – kind of like checking passports and inspecting baggage at the airport. If the balance of the inspection is in favor of danger, the NK cell is triggered to react.
The basic concept of cellular immunotherapy is to find ways to identify the best T cells and NK cells for this purpose, grow them to large numbers, and return them to patients where they can do their job attacking infection or cancer. The challenge with using NK cells to treat cancer is that there aren’t very many in our blood, chemotherapy damages them, and we need more of them to maintain their fight against cancer.
Our research found a way to get NK cells to grow in number. Treating patients with this approach requires growing them in a special facility that operates under special regulations called Good Manufacturing Practice. Our GMP-compliant facility is under construction and scheduled to open later this winter.
The Future for Cellular Immunotherapy
If T and NK cells are like assassins and border patrol, the keys to successfully fighting the invasion of cancer cells are to:
- Have enough of them
- Make sure they are well-trained to recognize the invaders
- Raise the body’s signals that put these cells on high alert
- Give them the ability to quickly locate the invaders
- Make sure the cancer cells don’t escape
Each one of these aspects is under investigation at Nationwide Children’s Hospital to make cellular therapy more effective against children’s cancer, and we are building the infrastructure necessary to bring these therapies to our patients. To find out more about our Center for Childhood Cancer, click here.