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

Autor: Fry TJ; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Shah NN; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Orentas RJ; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Stetler-Stevenson M; Laboratory of Pathology, Center for Cancer Research, NIH, Bethesda, Maryland, USA., Yuan CM; Laboratory of Pathology, Center for Cancer Research, NIH, Bethesda, Maryland, USA., Ramakrishna S; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Wolters P; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Martin S; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Delbrook C; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Yates B; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Shalabi H; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Fountaine TJ; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Shern JF; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Majzner RG; Department of Pediatrics, Stanford University, Stanford, California, USA., Stroncek DF; Department of Transfusion Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA., Sabatino M; Department of Transfusion Medicine, NIH Clinical Center, NIH, Bethesda, Maryland, USA., Feng Y; Cancer and Inflammation Program, National Cancer Institute, NIH, Bethesda, Maryland, USA., Dimitrov DS; Cancer and Inflammation Program, National Cancer Institute, NIH, Bethesda, Maryland, USA., Zhang L; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Nguyen S; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Qin H; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Dropulic B; Lentigen Corporation, Gaithersburg, Maryland, USA., Lee DW; Pediatric Oncology Branch, Center for Cancer Research, National Institutes of Health (NIH), Bethesda, Maryland, USA., Mackall CL; Department of Pediatrics and Standford Cancer Center, Stanford University, Stanford, California, USA.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2018 Jan; Vol. 24 (1), pp. 20-28. Date of Electronic Publication: 2017 Nov 20.
DOI: 10.1038/nm.4441
Abstrakt: 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 × 10 6 CD22-CAR T cells per kg body weight, including 5 of 5 patients with CD19 dim 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.
Databáze: MEDLINE
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