Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias

Renier J. Brentjens, Isabelle Rivière(Shanghai Cell Therapy Research Institute), Jae H. Park, Marco L. Davila, Xiuyan Wang(Shanghai Cell Therapy Research Institute), Jolanta Stefanski(Shanghai Cell Therapy Research Institute), Clare Taylor(Shanghai Cell Therapy Research Institute), Raymond Yeh, Shirley Bartido, Oriana Bórquez-Ojeda(Shanghai Cell Therapy Research Institute), Malgorzata Olszewska(Shanghai Cell Therapy Research Institute), Yvette Bernal, Hollie J. Pegram, Mark Przybylowski(Shanghai Cell Therapy Research Institute), Daniel Hollyman(Shanghai Cell Therapy Research Institute), Yelena Usachenko, Domenick Pirraglia(Shanghai Cell Therapy Research Institute), James Hosey(Shanghai Cell Therapy Research Institute), Elmer Santos, Elizabeth Halton, P. Maslak, David A. Scheinberg, Joseph G. Jurcic, Mark Heaney, Glenn Heller(Memorial Sloan Kettering Cancer Center), Mark G. Frattini, Michel Sadelain
Blood
August 18, 2011
10.1182/blood-2011-04-348540
Cited by 1,280Open Access
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Abstract

We report the findings from the first 10 patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) or relapsed B-cell acute lymphoblastic leukemia (ALL) we have enrolled for treatment with autologous T cells modified to express 19-28z, a second-generation chimeric antigen (Ag) receptor specific to the B-cell lineage Ag CD19. Eight of the 9 treated patients tolerated 19-28z(+) T-cell infusions well. Three of 4 evaluable patients with bulky CLL who received prior conditioning with cyclophosphamide exhibited either a significant reduction or a mixed response in lymphadenopathy without concomitant development of B-cell aplasia. In contrast, one patient with relapsed ALL who was treated in remission with a similar T-cell dose developed a predicted B-cell aplasia. The short-term persistence of infused T cells was enhanced by prior cyclophosphamide administration and inversely proportional to the peripheral blood tumor burden. Further analyses showed rapid trafficking of modified T cells to tumor and retained ex vivo cytotoxic potential of CD19-targeted T cells retrieved 8 days after infusion. We conclude that this adoptive T-cell approach is promising and more likely to show clinical benefit in the setting of prior conditioning chemotherapy and low tumor burden or minimal residual disease. These studies are registered at www.clinicaltrials.org as #NCT00466531 (CLL protocol) and #NCT01044069 (B-ALL protocol).

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