2012
DOI: 10.1158/1078-0432.ccr-11-1920
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The Future Is Now: Chimeric Antigen Receptors as New Targeted Therapies for Childhood Cancer

Abstract: Improved outcomes for children with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, gene therapy, and cell-processing technologies have paved the way for clinical applications of chimeric antigen receptor-based therapies. This is a new form of targeted immunotherapy that merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity, po… Show more

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Cited by 116 publications
(94 citation statements)
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“…Further analyses have revealed that mismatches for natural killer (NK) cell KIR/KIRligand genotypes and polymorphisms in the Fcγ receptor have also been associated with better responses to anti-GD2 immunotherapy [142,143]. With the significant side effects and known limitations of anti-GD2 antibody immunotherapy, many other immunologic approaches have been evaluated recently, including therapy with immunomodulatory CTLA4 checkpoint inhibitors [144], antitumor vaccines [145,146], and cell-based immunotherapy using either NK cells [147] or anti-GD2 targeted autologous T cells [148], which have been shown to have antitumor activity, including activity in cases with measurable disease [149,150]. Next-generation chimeric antigen receptor T cells, in which the constructs will include costimulatory domains to activate the T cell, are currently being developed [151].…”
Section: Treatment -Relapsed and Refractory Neuroblastomamentioning
confidence: 99%
“…Further analyses have revealed that mismatches for natural killer (NK) cell KIR/KIRligand genotypes and polymorphisms in the Fcγ receptor have also been associated with better responses to anti-GD2 immunotherapy [142,143]. With the significant side effects and known limitations of anti-GD2 antibody immunotherapy, many other immunologic approaches have been evaluated recently, including therapy with immunomodulatory CTLA4 checkpoint inhibitors [144], antitumor vaccines [145,146], and cell-based immunotherapy using either NK cells [147] or anti-GD2 targeted autologous T cells [148], which have been shown to have antitumor activity, including activity in cases with measurable disease [149,150]. Next-generation chimeric antigen receptor T cells, in which the constructs will include costimulatory domains to activate the T cell, are currently being developed [151].…”
Section: Treatment -Relapsed and Refractory Neuroblastomamentioning
confidence: 99%
“…General overviews of the genetic basis of ALL may be found in several recent excellent reviews (2)(3)(4)(5)(6). This review is part of a series of articles in this issue reviewing new genetic insights and therapeutic opportunities in childhood malignancies (7)(8)(9)(10)(11). Here, we briefly review key chromosomal rearrangements in ALL and then focus on several high-risk subtypes, which have hitherto been poorly understood and for which recent detailed genomic-profiling approaches are providing important insights into the genetic basis of disease, with potentially important implications for therapy.…”
Section: Acute Lymphoblastic Leukemiamentioning
confidence: 99%
“…In this approach, T cells are genetically modified ex vivo to express a CAR with the CD19 antigen recognition sequence of a monoclonal antibody linked to intracellular T-cell signaling domains (29,30). Modified T cells can recognize and kill the leukemic cells expressing the CD19 antigen.…”
Section: Discussionmentioning
confidence: 99%