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Clinical practice: chimeric antigen receptor (CAR) T cells: a major breakthrough in the battle against cancer.
Lundh, Stefan; Jung, In-Young; Dimitri, Alexander; Vora, Anish; Melenhorst, J Joseph; Jadlowsky, Julie K; Fraietta, Joseph A.
Afiliação
  • Lundh S; Center for Cellular Immunotherapies, University of Pennsylvania, South Pavilion Expansion, Room 9-104, 3400 Civic Center Blvd., Bldg. 421, Philadelphia, PA, 19104, USA.
  • Jung IY; Center for Cellular Immunotherapies, University of Pennsylvania, South Pavilion Expansion, Room 9-104, 3400 Civic Center Blvd., Bldg. 421, Philadelphia, PA, 19104, USA.
  • Dimitri A; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Vora A; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Melenhorst JJ; Center for Cellular Immunotherapies, University of Pennsylvania, South Pavilion Expansion, Room 9-104, 3400 Civic Center Blvd., Bldg. 421, Philadelphia, PA, 19104, USA.
  • Jadlowsky JK; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Fraietta JA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Clin Exp Med ; 20(4): 469-480, 2020 Nov.
Article em En | MEDLINE | ID: mdl-32333215
ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy has come of age, offering a potentially curative option for patients who are refractory to standard anti-cancer treatments. The success of CAR T cell therapy in the setting of acute lymphoblastic leukemia and specific types of B cell lymphoma led to rapid regulatory approvals of CD19-directed CAR T cells, first in the United States and subsequently across the globe. Despite these major milestones in the field of immuno-oncology, growing experience with CAR T cells has also highlighted the major limitations of this strategy, namely challenges associated with manufacturing a bespoke patient-specific product, intrinsic immune cell defects leading to poor CAR T cell function as well as persistence, and/or tumor cell resistance resulting from loss or modulation of the targeted antigen. In addition, both on- and off-tumor immunotoxicities and the financial burden inherent in conventional cellular biomanufacturing often hamper the success of CAR T cell-based treatment approaches. Herein, we provide an overview of the opportunities and challenges related to the first form of gene transfer therapy to gain commercial approval in the United States. Ongoing advances in the areas of genetic engineering, precision genome editing, toxicity mitigation methods and cell manufacturing will improve the efficacy and safety of CAR T cells for hematologic malignancies and expand the use of this novel class of therapeutics to reach solid tumors.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Imunoterapia Adotiva / Neoplasias Hematológicas / Receptores de Antígenos Quiméricos Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Imunoterapia Adotiva / Neoplasias Hematológicas / Receptores de Antígenos Quiméricos Idioma: En Ano de publicação: 2020 Tipo de documento: Article