Engineering a Complex TCR Immunotherapy.

• Position: LEUKEMIA RELAPSE - T-cell receptors

A novel way to engineer T cells genetically that may be effective for treating and preventing leukemia relapse has been developed by scientists at the Fred Hutchinson Cancer Research Center, Seattle, Wash., and the University of Washington.

The findings, published in the journal Blood, provide the basis for launching a first-in-human clinical trial of this new immunotherapy, which relies on engineered T-cell receptors (TCRs). This immunotherapy represents a different method of genetic engineering than the CAR T-cell therapies that have been approved by the Food and Drug Administration.

Relapse occurs in about one-third of patients with acute leukemia who undergo stem cell transplantation to rebuild cancer-free blood cells, and more than 90% of these patients die after an average survival of about four months.

"New therapies are desperately needed to prevent and treat relapse of leukemia in patients who have undergone hematopoietic stem cell transplantation' says pediatric oncologist Marie Bleakley, the papers senior author and a member of Hutch's Clinical Research Division.

T cells, a linchpin of the immune system, have a variety of molecules on their surface, known as receptors, which recognize cells that are foreign or diseased and kill them. To boost the immune system's ability to recognize and attack these "invaders," researchers may transfer genes for a tumor-specific T-cell receptor into the T cells collected from a patient's transplant donor.

In this work, Bleakley and colleagues exploited a specific "minor histocompatibility antigen," or minor H antigen, found on the surface of leukemia cells in some patients. Using this group of antigens as targets is being reexamined now that the basic principles of cancer immunotherapy are better understood and potent T-cell immunotherapy is a clinical reality. Because...