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Nat Med. 2018 Jan;24(1):20-28. doi: 10.1038/nm.4441. Epub 2017 Nov 20.

CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy.

Author information

1
Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA.
2
Laboratory of Pathology, Center for Cancer Research, NIH, Bethesda, Maryland, USA.
3
Department of Pediatrics, Stanford University, Stanford, California, USA.
4
Department of Transfusion Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA.
5
Cancer and Inflammation Program, National Cancer Institute, NIH, Bethesda, Maryland, USA.
6
Lentigen Corporation, Gaithersburg, Maryland, USA.
7
Department of Pediatrics and Standford Cancer Center, Stanford University, Stanford, California, USA.

Abstract

Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. Dose-dependent antileukemic activity was observed, with complete remission obtained in 73% (11/15) of patients receiving ≥1 × 106 CD22-CAR T cells per kg body weight, including 5 of 5 patients with CD19dim or CD19- B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted CD22+ cell escape from killing by CD22-CAR T cells. These results are the first to establish the clinical activity of a CD22-CAR in B-ALL, including leukemia resistant to anti-CD19 immunotherapy, demonstrating potency against B-ALL comparable to that of CD19-CAR at biologically active doses. Our results also highlight the critical role played by antigen density in regulating CAR function.

PMID:
29155426
PMCID:
PMC5774642
DOI:
10.1038/nm.4441
[Indexed for MEDLINE]
Free PMC Article

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