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2015 ; 125
(9
): 3392-400
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CAR therapy: the CD19 paradigm
#MMPMID26325036
Sadelain M
J Clin Invest
2015[Sep]; 125
(9
): 3392-400
PMID26325036
show ga
Twenty-five years after its inception, the genetic engineering of T cells is now
a therapeutic modality pursued at an increasing number of medical centers. This
immunotherapeutic strategy is predicated on gene transfer technology to instruct
T lymphocytes to recognize and reject tumor cells. Chimeric antigen receptors
(CARs) are synthetic receptors that mediate antigen recognition, T cell
activation, and - in the case of second-generation CARs - costimulation to
augment T cell functionality and persistence. We demonstrated over a decade ago
that human T cells engineered with a CD19-specific CAR eradicated B cell
malignancies in mice. Several phase I clinical trials eventually yielded dramatic
results in patients with leukemia or lymphoma, especially acute lymphoblastic
leukemia (ALL). This review recounts the milestones of CD19 CAR therapy and
summarizes lessons learned from the CD19 paradigm.