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Cell-ebrating the Use of Designer T Cells and NK Cells

CCH Newsletter - Fall 2010

During the past 40 years, chemotherapy, radiation therapy and surgery have brought the overall cure rate for childhood cancer to nearly 80%. However, for high-risk, relapsed, and advanced childhood cancers, these conventional therapies have reached a point of diminishing returns.

The future of pediatric oncology rests in understanding the mechanisms behind cancer cells’ ability to resist chemotherapy and developing new therapies that do not rely on chemotherapy. One approach is harnessing a child’s immune system to be able to fight back against cancer cells.

At MD Anderson Children’s Cancer Hospital, the pediatric cell therapy team has been investigating the use of designer T cells and natural killer (NK) cells to tip the scales in the patient’s favor. Immunotherapies that began in the laboratory are now being translated to clinical trials for children, with hopes that high-risk patients will have increased potential to overcome their cancer.

Harnessing T cells

T cells are a major source of immune cells that a human body relies on for detecting and destroying abnormal cells. Most times, a patient’s cancer learns to disguise itself and hide from the patient’s T cells, leaving an ineffective immune system.

Laurence Cooper, M.D., Ph.D., from the Children’s Cancer Hospital, has engineered a way to genetically alter T cells so that they are tumor specific and have an improved ability to seek out and destroy cancerous cells while leaving normal cells alone. Using a gene transfer approach called Sleeping Beauty, Cooper and his team have introduced an immuno-receptor into human T cells to redirect the cells’ specificity to a panel of tumor-cell types. Some of the genetically modified T cells are specific to CD19, a receptor found on B-cell leukemia and lymphoma. As a result, they have opened a clinical trial to infuse tumor-specific T cells into patients with these B-cell malignancies.

Having the capability to genetically alter T cells allows MD Anderson researchers to potentially improve the graft-versus-leukemia (GVL) effect after bone marrow transplantation and, in particular, after umbilical cord transplantation. Currently, researchers take a small portion of the umbilical cord blood prior to transplantation and use this as a source of T cells to render them specific for CD19. After a patient receives an umbilical cord transplant, he or she would receive an infusion of the genetically modified T cells to improve the GVL effect. Researchers hope this booster infusion will add another line of defense against any remaining cancer cells.

Expanding NK Cells

NK cells are another form of immune cells that the body uses to combat cancer. Researchers at the Children’s Cancer Hospital have generated artificial antigen presenting cells (aAPC) that function as nurse cells to grow the number of NK cells within a short period of time. This technology is being adapted for clinical use to expand NK cells in cord blood and peripheral blood.

In addition, researchers are investigating ways to attach homing receptors to aAPC to help direct NK cells where they need to go, whether it’s the lymph nodes, brain tissue, bone marrow or other areas.

In the past year, the Children’s Cancer Hospital has opened three clinical trials to test the ability of NK cells to prolong event-free survival. Patients are infused with NK cells from a related donor for the treatment of acute lymphocytic leukemia, acute myeloid leukemia and neuroblastoma.

Enhancing the AYA experience

There are a growing number of adolescents and young adults (AYA) being treated with cell therapy and stem cell transplantation at MD Anderson. To better meet the unique needs of this special patient population, the Pediatric Cell Therapy team now oversees the inpatient care of all MD Anderson patients 25 years old and younger needing stem cell transplantation. The Pediatric Cell Therapy program transplants approximately 80 to 90 patients a year.

In addition to the comprehensive medical care tailored to the AYA population, these patients benefit from a variety of specialized services offered through the Children’s Cancer Hospital for their age group, such as an in-hospital school and education program, vocational counseling, peer-to-peer interaction, events and an AYA Advisory Council consisting of patients and staff.

© 2015 The University of Texas MD Anderson Cancer Center