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This Week in NEJM: Aug 11, 2011

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In NEJM this week, researchers at the University of Pennsylvania's Perelman School of Medicine present a report on their use of chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. The team initiated a pilot clinical trial of treatment with autologous T cells, expressing an anti-CD19 chimeric antigen receptor, and treated three CLL patients. One of the patients, who had advanced p53-deficient CLL, improved with treatment to the point where there was no longer any evidence of CLL in the bone marrow 23 days after treatment. "The karyotype was now normal in 15 of 15 cells, and FISH testing was negative for deletion TP53 in 198 of 200 cells examined; this is considered to be within normal limits in negative controls," the authors write. "Flow-cytometric analysis showed no residual CLL, and B cells were not detectable. CT scanning performed on day 31 after infusion showed resolution of adenopathy." In addition, CTs from three months after T-cell infusion showed sustained remission in the patient, and remission has lasted for 10 months so far. "Unlike antibody-mediated therapy, chimeric antigen receptor–modified T cells have the potential to replicate in vivo, and long-term persistence could lead to sustained tumor control," the team adds. "Two other patients with advanced CLL have also received CART19 infusions according to this protocol, and all three have had tumor responses. These findings warrant continued study of CD19-redirected T cells for B-cell neoplasms."

In a related editorial in NEJM, Providence Cancer Center's Walter Urba and the National Institute on Aging's Dan Longo write that redirecting T cells by gene transfer of T-cell receptors with predefined antigen specificity could overcome some of the challenges involved in using tumor-infiltrating lymphocytes in the clinic. In addition, the parallel strategy of redirecting T cells with chimeric antigen receptors has theoretical advantages over other T-cell based therapies. In referring to the T-cell study in this week's NEJM, Urba and Longo call the results "impressive," but add that "only with the more widespread clinical use of chimeric antigen–receptor T cells will we learn whether the results reported by Porter et al. reflect an authentic advance toward a clinically applicable and effective therapy or yet another promising lead that runs into a barrier that cannot be easily overcome."

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