Frontiers in Immunology (Aug 2020)
Automated Manufacture of Autologous CD19 CAR-T Cells for Treatment of Non-hodgkin Lymphoma
- Zachary Jackson,
- Anne Roe,
- Ashish Arunkumar Sharma,
- Filipa Blasco Tavares Pereira Lopes,
- Aarthi Talla,
- Sarah Kleinsorge-Block,
- Kayla Zamborsky,
- Jennifer Schiavone,
- Shivaprasad Manjappa,
- Robert Schauner,
- Grace Lee,
- Ruifu Liu,
- Paolo F. Caimi,
- Paolo F. Caimi,
- Ying Xiong,
- Winfried Krueger,
- Andrew Worden,
- Mike Kadan,
- Dina Schneider,
- Rimas Orentas,
- Rimas Orentas,
- Boro Dropulic,
- Rafick-Pierre Sekaly,
- Marcos de Lima,
- Marcos de Lima,
- David N. Wald,
- David N. Wald,
- David N. Wald,
- Jane S. Reese,
- Jane S. Reese
Affiliations
- Zachary Jackson
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- Anne Roe
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- Ashish Arunkumar Sharma
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- Filipa Blasco Tavares Pereira Lopes
- Department of Nutrition, Case Western Reserve University, Cleveland, OH, United States
- Aarthi Talla
- The Alan Turing Institute, British Library, London, United Kingdom
- Sarah Kleinsorge-Block
- Stem Cell Transplantation Program, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Kayla Zamborsky
- Stem Cell Transplantation Program, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Jennifer Schiavone
- Stem Cell Transplantation Program, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Shivaprasad Manjappa
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Robert Schauner
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- Grace Lee
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- Ruifu Liu
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- Paolo F. Caimi
- Stem Cell Transplantation Program, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Paolo F. Caimi
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Ying Xiong
- Lentigen Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, United States
- Winfried Krueger
- Lentigen Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, United States
- Andrew Worden
- Lentigen Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, United States
- Mike Kadan
- Lentigen Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, United States
- Dina Schneider
- Lentigen Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, United States
- Rimas Orentas
- Department of Pediatrics, Seattle Children’s Research Institute, Seattle, WA, United States
- Rimas Orentas
- Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States
- Boro Dropulic
- Lentigen Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, United States
- Rafick-Pierre Sekaly
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- Marcos de Lima
- Stem Cell Transplantation Program, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Marcos de Lima
- Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- David N. Wald
- Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
- David N. Wald
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- David N. Wald
- 0Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States
- Jane S. Reese
- Stem Cell Transplantation Program, University Hospitals Seidman Cancer Center, Cleveland, OH, United States
- Jane S. Reese
- 0Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, United States
- DOI
- https://doi.org/10.3389/fimmu.2020.01941
- Journal volume & issue
-
Vol. 11
Abstract
Chimeric antigen receptor T cells (CAR-T cell) targeting CD19 are effective against several subtypes of CD19-expressing hematologic malignancies. Centralized manufacturing has allowed rapid expansion of this cellular therapy, but it may be associated with treatment delays due to the required logistics. We hypothesized that point of care manufacturing of CAR-T cells on the automated CliniMACS Prodigy® device allows reproducible and fast delivery of cells for the treatment of patients with non-Hodgkin lymphoma. Here we describe cell manufacturing results and characterize the phenotype and effector function of CAR-T cells used in a phase I/II study. We utilized a lentiviral vector delivering a second-generation CD19 CAR construct with 4-1BB costimulatory domain and TNFRSF19 transmembrane domain. Our data highlight the successful generation of CAR-T cells at numbers sufficient for all patients treated, a shortened duration of production from 12 to 8 days followed by fresh infusion into patients, and the detection of CAR-T cells in patient circulation up to 1-year post-infusion.
Keywords
