Chimeric Receptor-Modified T-Cells Show Potential in CLL

Wednesday, August 10, 2011 (Last Updated: 08/11/2011)

WEDNESDAY, Aug. 10 (HealthDay News) -- Autologous T-cells expressing an anti-CD19 chimeric antigen receptor (CART19) have the potential for in vivo proliferation, and long-term persistence in patients with chronic lymphoid leukemia (CLL), according to a study published online Aug. 10 in the New England Journal of Medicine.

David L. Porter, M.D., from the University of Pennsylvania in Philadelphia, and colleagues investigated the immunologic and clinical effects of in vivo T-cell treatment with a chimeric antigen receptor in a patient with advanced, p53-deficient CLL. Autologous T-cells from the patient were genetically modified to target B-cell antigen CD19 through transduction with a lentivirus vector expressing anti-CD19 linked to CD137 (costimulatory receptor) and CD3-zeta (signal-transduction component) signaling domains, and the safety and feasibility of the approach was assessed.

The investigators found that the CART19 cells expanded to more than 1,000 times their initial engraftment level in vivo, with delayed development of tumor lysis syndrome, and complete remission. Lymphopenia and delayed tumor lysis syndrome were the only grade 3/4 toxic effects reported. High levels of modified T-cells persisted in blood and bone marrow for six months, and continued to express chimeric antigen receptor. The bone marrow showed a specific immune response along with loss of normal B-cells and leukemia cells expressing for CD19. Remission was persistent 10 months after treatment and, as expected, hypogammaglobulinemia was a chronic toxic effect.

"Chimeric antigen receptor-modified T-cells have the potential to replicate in vivo, and long-term persistence could lead to sustained tumor control," the authors write.

Several study authors disclosed financial relationships with the pharmaceutical and biotechnology industries. One editorial author disclosed a financial relationship with Bristol-Myers Squibb.

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Specialties Hematology & Oncology

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