Using T-cells to Defeat Childhood Cancer
Led by Dr. Michael Jensen of the Ben Towne Center for Childhood Cancer Research, Seattle Children’s researchers are advancing immunotherapy, which uses the body’s immune system to eradicate cancer without the debilitating side effects of chemotherapy or radiation.
The therapy’s active ingredients are T-cells, a type of white blood cell that protects the body from infection. A T-cell works by bumping up against a cell with a virus hiding inside it. Then, the T-cell drills holes in the membrane of the virally infected cell and transfers little packets of protein that literally make the infected cell dissolve. The Jensen Lab is working to apply this approach to cancer.
Since cancer cells start out as healthy cells, T-cells don’t recognize them as threats, leaving cancer free to overtake its victims. Seattle Children’s researchers are working to reprogram T-cells so that they have the ability to kill cancer cells with a laser-like focus – an approach that eliminates the need for potentially damaging surgery, chemotherapy and radiation.
The reprogramming approach relies on recombinant DNA technology, which allows a segment of DNA to be taken out of a chromosome in a T-cell and replaced with “engineered” DNA that fights cancer. Eventually, researchers envision creating a library of engineered DNA molecules that would fight different types of childhood cancers.
Cancer Immunotherapy: Frequently Asked Questions
What is the process used to reprogram a T-cell?
The process involves taking a tube of a patient’s own blood and isolating the T-cells; inserting genetically engineered pieces of DNA into the T-cells that carry instructions to recognize cancer cells as threats and destroy them; growing billions of identical, reprogrammed T-cells in an incubator in our research facility; then, re-infusing them in the patient.
Why is it important to do pediatric research on the T-cell approach?
The types of cancers that occur in children do not have the same set of markers on them as adult cancers. If researchers only did the T-cell engineering on adult cancers, they would not know how to reprogram the DNA molecules in T-cells to fight childhood cancers.
Also, children’s immune systems tend to be very healthy, even among children with cancer. This may allow the T-cells to be more easily reprogrammed and multiplied outside the body before they are re-infused in patients.
How long does it take to grow the reprogrammed T-cells?
Currently, the process to produce a bag of reprogrammed T-cells for a patient takes three months. As clinical trials and research progress, the hope is that this process will be shortened to a week.
Has this research been successful to date with T-cell engineering?
Before coming to Seattle Children’s, Jensen demonstrated T-cell therapy’s powerful potential as a researcher at City of Hope. In his laboratory studies, reprogrammed T-cells killed brain-tumor cells in a petri dish in 45 minutes.
In animal trials, mice who received T-cells that weren’t reprogrammed had tumors that continued to grow. The mice who received a single dose of the reprogrammed T-cells were all cured within two or three days of receiving the T-cell therapy. These mice had no symptoms during treatment and none of their tumors came back.
Jensen also conducted the first-ever FDA-authorized human trial of this T-cell therapy in adults with lymphoma as well as in children who had recurrent neuroblastoma. One patient’s growing brain tumor responded completely to the T-cell infusions with no worse side effect than feeling like he had a cold. The data from these safety trials indicate that reengineered T-cells don’t cause harm to the human body.
Where will the T-cell engineering take place?
Phase I and II trials for the T-cell engineering will take place at the Ben Towne Center for Childhood Cancer Research and in the Therapeutic Cell Production Core, a high-tech laboratory that is among a small handful of pediatric facilities meeting the FDA’s strict requirements for manufacturing therapies.
Read about a new Phase I trial: A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia.