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CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial.
Spiegel, Jay Y; Patel, Shabnum; Muffly, Lori; Hossain, Nasheed M; Oak, Jean; Baird, John H; Frank, Matthew J; Shiraz, Parveen; Sahaf, Bita; Craig, Juliana; Iglesias, Maria; Younes, Sheren; Natkunam, Yasodha; Ozawa, Michael G; Yang, Eric; Tamaresis, John; Chinnasamy, Harshini; Ehlinger, Zach; Reynolds, Warren; Lynn, Rachel; Rotiroti, Maria Caterina; Gkitsas, Nikolaos; Arai, Sally; Johnston, Laura; Lowsky, Robert; Majzner, Robbie G; Meyer, Everett; Negrin, Robert S; Rezvani, Andrew R; Sidana, Surbhi; Shizuru, Judith; Weng, Wen-Kai; Mullins, Chelsea; Jacob, Allison; Kirsch, Ilan; Bazzano, Magali; Zhou, Jing; Mackay, Sean; Bornheimer, Scott J; Schultz, Liora; Ramakrishna, Sneha; Davis, Kara L; Kong, Katherine A; Shah, Nirali N; Qin, Haiying; Fry, Terry; Feldman, Steven; Mackall, Crystal L; Miklos, David B.
Afiliação
  • Spiegel JY; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Patel S; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Muffly L; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Hossain NM; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Oak J; Division of Hematology/Oncology, Loyola University Medical Center, Chicago, IL, USA.
  • Baird JH; Department of Clinical Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Frank MJ; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Shiraz P; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Sahaf B; Division of Blood and Marrow Transplantation and Cellular Therapy, 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.
  • Iglesias M; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Younes S; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Natkunam Y; Department of Clinical Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Ozawa MG; Department of Clinical Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Yang E; Department of Clinical Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Tamaresis J; Department of Clinical Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Chinnasamy H; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
  • Ehlinger Z; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Reynolds W; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Lynn R; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Rotiroti MC; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Gkitsas N; Lyell Immunopharma, San Francisco, CA, USA.
  • Arai S; Department of Pediatrics-Hematology/Oncology, Stanford University School of Medicine, Stanford, CA, USA.
  • Johnston L; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Lowsky R; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Majzner RG; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Meyer E; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Negrin RS; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Rezvani AR; Department of Pediatrics-Hematology/Oncology, Stanford University School of Medicine, Stanford, CA, USA.
  • Sidana S; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Shizuru J; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Weng WK; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Mullins C; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Jacob A; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Kirsch I; Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine, Stanford, CA, USA.
  • Bazzano M; Adaptive Biotechnologies, Seattle, WA, USA.
  • Zhou J; Adaptive Biotechnologies, Seattle, WA, USA.
  • Mackay S; Adaptive Biotechnologies, Seattle, WA, USA.
  • Bornheimer SJ; IsoPlexis, Brantford, CT, USA.
  • Schultz L; IsoPlexis, Brantford, CT, USA.
  • Ramakrishna S; IsoPlexis, Brantford, CT, USA.
  • Davis KL; BD Biosciences, San Jose, CA, USA.
  • Kong KA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Shah NN; Department of Pediatrics-Hematology/Oncology, Stanford University School of Medicine, Stanford, CA, USA.
  • Qin H; Pediatric Oncology Branch Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA.
  • Fry T; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Feldman S; Department of Pediatrics-Hematology/Oncology, Stanford University School of Medicine, Stanford, CA, USA.
  • Mackall CL; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Miklos DB; Department of Pediatrics-Hematology/Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Nat Med ; 27(8): 1419-1431, 2021 08.
Article em En | MEDLINE | ID: mdl-34312556
ABSTRACT
Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19- or CD19lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial ( NCT03233854 ) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n = 17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n = 21), 62% of patients responded with 29% CR. Relapses were CD19-/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22-/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imunoterapia Adotiva / Linfoma de Células B / Antígenos CD19 / Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico Tipo de estudo: Guideline Limite: Adult / Aged / Humans / Middle aged Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imunoterapia Adotiva / Linfoma de Células B / Antígenos CD19 / Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico Tipo de estudo: Guideline Limite: Adult / Aged / Humans / Middle aged Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos