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Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia.
Orlando, Elena J; Han, Xia; Tribouley, Catherine; Wood, Patricia A; Leary, Rebecca J; Riester, Markus; Levine, John E; Qayed, Muna; Grupp, Stephan A; Boyer, Michael; De Moerloose, Barbara; Nemecek, Eneida R; Bittencourt, Henrique; Hiramatsu, Hidefumi; Buechner, Jochen; Davies, Stella M; Verneris, Michael R; Nguyen, Kevin; Brogdon, Jennifer L; Bitter, Hans; Morrissey, Michael; Pierog, Piotr; Pantano, Serafino; Engelman, Jeffrey A; Winckler, Wendy.
Affiliation
  • Orlando EJ; Novartis Institutes for BioMedical Research, Cambridge, MA, USA. elena.orlando@novartis.com.
  • Han X; Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
  • Tribouley C; Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
  • Wood PA; Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
  • Leary RJ; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Riester M; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Levine JE; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Qayed M; Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA, USA.
  • Grupp SA; Divison of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Boyer M; University of Utah, Salt Lake City, UT, USA.
  • De Moerloose B; Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
  • Nemecek ER; Oregon Health & Science University, Portland, OR, USA.
  • Bittencourt H; Sainte-Justine University Health Center, Montreal, Quebec, Canada.
  • Hiramatsu H; Department of Pediatrics, Kyoto University, Kyoto, Japan.
  • Buechner J; Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway.
  • Davies SM; Divison of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Verneris MR; Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
  • Nguyen K; Navigate BioPharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA, USA.
  • Brogdon JL; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Bitter H; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Morrissey M; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Pierog P; Novartis Pharmaceutical Corporation, East Hanover, NJ, USA.
  • Pantano S; Novartis Pharma AG, Basel, Switzerland.
  • Engelman JA; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
  • Winckler W; Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
Nat Med ; 24(10): 1504-1506, 2018 10.
Article in En | MEDLINE | ID: mdl-30275569
ABSTRACT
We identified genetic mutations in CD19 and loss of heterozygosity at the time of CD19- relapse to chimeric antigen receptor (CAR) therapy. The mutations are present in the vast majority of resistant tumor cells and are predicted to lead to a truncated protein with a nonfunctional or absent transmembrane domain and consequently to a loss of surface antigen. This irreversible loss of CD19 advocates for an alternative targeting or combination CAR approach.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Drug Resistance, Neoplasm / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Receptors, Chimeric Antigen Limits: Humans Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2018 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / Drug Resistance, Neoplasm / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Receptors, Chimeric Antigen Limits: Humans Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2018 Document type: Article Affiliation country: