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Post-infusion CAR TReg cells identify patients resistant to CD19-CAR therapy.
Good, Zinaida; Spiegel, Jay Y; Sahaf, Bita; Malipatlolla, Meena B; Ehlinger, Zach J; Kurra, Sreevidya; Desai, Moksha H; Reynolds, Warren D; Wong Lin, Anita; Vandris, Panayiotis; Wu, Fang; Prabhu, Snehit; Hamilton, Mark P; Tamaresis, John S; Hanson, Paul J; Patel, Shabnum; Feldman, Steven A; Frank, Matthew J; Baird, John H; Muffly, Lori; Claire, Gursharan K; Craig, Juliana; Kong, Katherine A; Wagh, Dhananjay; Coller, John; Bendall, Sean C; Tibshirani, Robert J; Plevritis, Sylvia K; Miklos, David B; Mackall, Crystal L.
Afiliación
  • Good Z; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Spiegel JY; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
  • Sahaf B; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Malipatlolla MB; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Ehlinger ZJ; Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Kurra S; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
  • Desai MH; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Reynolds WD; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Wong Lin A; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Vandris P; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Wu F; Homer Stryker M.D. School of Medicine, Western Michigan University, Kalamazoo, MI, USA.
  • Prabhu S; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Hamilton MP; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Tamaresis JS; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Hanson PJ; Cancer Research Lab, Flow Cytometry Core Facility, University of California, Berkeley, Berkeley, CA, USA.
  • Patel S; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Feldman SA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Frank MJ; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Baird JH; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Muffly L; Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Claire GK; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
  • Craig J; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Kong KA; Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Wagh D; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Coller J; Laboratory for Cell and Gene Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Bendall SC; Syncopation Life Sciences, San Mateo, CA, USA.
  • Tibshirani RJ; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Plevritis SK; Laboratory for Cell and Gene Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Miklos DB; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Mackall CL; Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
Nat Med ; 28(9): 1860-1871, 2022 09.
Article en En | MEDLINE | ID: mdl-36097223
ABSTRACT
Approximately 60% of patients with large B cell lymphoma treated with chimeric antigen receptor (CAR) T cell therapies targeting CD19 experience disease progression, and neurotoxicity remains a challenge. Biomarkers associated with resistance and toxicity are limited. In this study, single-cell proteomic profiling of circulating CAR T cells in 32 patients treated with CD19-CAR identified that CD4+Helios+ CAR T cells on day 7 after infusion are associated with progressive disease and less severe neurotoxicity. Deep profiling demonstrated that this population is non-clonal and manifests hallmark features of T regulatory (TReg) cells. Validation cohort analysis upheld the link between higher CAR TReg cells with clinical progression and less severe neurotoxicity. A model combining expansion of this subset with lactate dehydrogenase levels, as a surrogate for tumor burden, was superior for predicting durable clinical response compared to models relying on each feature alone. These data credential CAR TReg cell expansion as a novel biomarker of response and toxicity after CAR T cell therapy and raise the prospect that this subset may regulate CAR T cell responses in humans.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de Neurotoxicidad / Receptores Quiméricos de Antígenos Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndromes de Neurotoxicidad / Receptores Quiméricos de Antígenos Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos