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Dual Targeting of Mesothelin and CD19 with Chimeric Antigen Receptor-Modified T Cells in Patients with Metastatic Pancreatic Cancer.
Ko, Andrew H; Jordan, Alexander C; Tooker, Evan; Lacey, Simon F; Chang, Renee B; Li, Yan; Venook, Alan P; Tempero, Margaret; Damon, Lloyd; Fong, Lawrence; O'Hara, Mark H; Levine, Bruce L; Melenhorst, J Joseph; Plesa, Gabriela; June, Carl H; Beatty, Gregory L.
Afiliação
  • Ko AH; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Jordan AC; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Tooker E; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Lacey SF; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
  • Chang RB; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Li Y; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Venook AP; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Tempero M; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Damon L; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Fong L; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • O'Hara MH; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Levine BL; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
  • Melenhorst JJ; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Plesa G; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
  • June CH; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Beatty GL; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Mol Ther ; 28(11): 2367-2378, 2020 11 04.
Article em En | MEDLINE | ID: mdl-32730744
ABSTRACT
B cells infiltrate pancreatic ductal adenocarcinoma (PDAC) and in preclinical cancer models, can suppress T cell immunosurveillance in cancer. Here, we conducted a pilot study to assess the safety and feasibility of administering lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin to target tumor cells along with CART cells redirected against CD19 to deplete B cells. Both CARs contained 4-1BB and CD3ζ signaling domains. Three patients with chemotherapy-refractory PDAC received 1.5 g/m2 cyclophosphamide prior to separate infusions of lentiviral-transduced T cells engineered to express chimeric anti-mesothelin immunoreceptor SS1 (CART-Meso, 3 × 107/m2) and chimeric anti-CD19 immunoreceptor (CART-19, 3 × 107/m2). Treatment was well tolerated without dose-limiting toxicities. Best response was stable disease (1 of 3 patients). CART-19 (compared to CART-Meso) cells showed the greatest expansion in the blood, although persistence was transient. B cells were successfully depleted in all subjects, became undetectable by 7-10 days post-infusion, and remained undetectable for at least 28 days. Together, concomitant delivery of CART-Meso and CART-19 cells in patients with PDAC is safe. CART-19 cells deplete normal B cells but at the dose tested in these 3 subjects did not improve CART-Meso cell persistence.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Linfócitos T / Imunoterapia Adotiva / Antígenos CD19 / Proteínas Ligadas por GPI / Receptores de Antígenos Quiméricos Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Linfócitos T / Imunoterapia Adotiva / Antígenos CD19 / Proteínas Ligadas por GPI / Receptores de Antígenos Quiméricos Idioma: En Ano de publicação: 2020 Tipo de documento: Article