Younger T cells improve immunotherapy for Children's Cancer

Pediatric oncologists from The Children's Hospital of Philadelphia (CHOP) have investigated techniques to improve and broaden a novel personalized cell therapy to treat children with cancer. The researchers say that a patient's outcome may be improved if clinicians select specific subtypes of T cells to attack diseases like acute lymphoblastic leukemia (ALL) and lymphoma.
"Our main finding is that younger T cells are critically important in T cell immunotherapy," said pediatric oncologist David M. Barrett, M.D., Ph.D., at The Children's Hospital of Philadelphia. "Collecting and expanding these cells could increase the number of children with cancer who could benefit from this innovative treatment." The T cell therapy, developed with Barrett's and Grupp's collaborators at the Perelman School of Medicine at the University of Pennsylvania, is a form of immunotherapy, manipulating the body's own immune system. Specifically, the scientists modify T cells, the workhorses of the body's immune system, to attack B cells, other immune cells that become cancerous in specific cancers such as ALL. The researchers first extract a patient's own T cells and reprogram them to hunt down and eliminate B cells after those modified T cells are returned to the patient. Barrett and colleagues followed 50 child and adolescent patients in a clinical trial of B-cell cancers at CHOP, of whom 38 had ALL and 12 had non-Hodgkin's lymphoma (NHL). The study team measured immune system markers and fully characterized their T cell populations once a month for six months following a patient's initial diagnosis. The study team found that early-lineage T cells, classified as either naive T cells (newly minted cells) or stem central memory T cells (self-renewing, highly proliferative cells) were the most effective in immunotherapy. Those early-lineage T cells also expanded best in the laboratory, before they were returned to each patient for T cell therapy.
Significantly, early-lineage T cells were also more vulnerable to chemotherapy than older cells.