Children’s Mercy is testing a new weapon in the fight against neuroblastoma.
Designed and directed by Doug Myers, MD, hematologist/oncologist, and associate professor of pediatrics at the University of Missouri-Kansas City School of Medicine, a clinical trial using a pair of cell-based immunotherapies to attack specific tumors is under way.
|Doug Myers, MD
The trial builds on previous investigations that use chimeric T-cell receptors to target GD2 on the surface of neuroblastoma cells. The new trial involves a bone marrow transplant from the parent to remove lymphocytes from the patient’s system and create an environment in which the altered T-cells can increase and multiply.
Using T-cells to Enhance Neuroblastoma Treatment
This strategy is designed to promote multiplication of tumor-targeting T-cells that provides a sustained effect. A potential benefit is the immune system of the parent, given through the transplant process, may provide an immune mediated attack against the tumor.
“Early studies found that the modified T-cells disappeared to levels we could hardly detect,” said Dr. Myers. “I wondered what would happen if we made the environment and the patient more conducive to the cells growing in number. What if we depleted the body of the other lymphocytes so the ones we infused would find themselves in a vacuum with plenty of room to expand, so to speak?”
Dr. Myers believes that emptying the body of T-cells will give the infused cells an opportunity to expand and fill the space. The bone marrow transplant, from parent to child, removes lymphocytes from the patient and bone marrow transplant product.
Training T-cells to Destroy Tumor Cells
Lymphocytes in additional blood taken from the donor are separated, and a gene is delivered into the lymphocytes that codes for a chimeric T-cell receptor that is specific for the GD2 target on the tumor.
The modified lymphocytes are infused into the patient around 30 days after the bone marrow transplant.
The expectation is that T-cells expressing the new receptor will now recognize the tumor, attach to GD2 on the tumor, and then signal the T-cell to kill tumor cells.
Early Results are Encouraging
The first patient to undergo the treatment had an immediate response, with a reduction in tumors. Pain medication was eliminated, and the patient regained mobility to play basketball and return to school. Unfortunately, six months after the treatment the tumors returned.
“We were very excited about the response we did get, but of course, disappointed that it wasn’t enough to produce a cure,” said Dr. Myers. “We were able to show our patient had no toxicity from either the transplant or the infused cells, and in contrast to previous single-therapy studies, with our combined approach, the genetically modified T-cells expanded very well.”
How We're Planning to Expand T-cell Research
Additional trials of the combined therapies are planned.
“Because of the significant tumor response achieved in the first trial, we’re investigating what will happen if we have less tumor burden to begin with,”
Dr. Myers added. “The additional patients joining the trial don’t have nearly the amount of tumor as our first patient, and we hope that will allow us to produce a better result.”
Dr. Myers anticipates that should the approach prove effective, similar treatments could be employed against other GD2 expressing tumors.