학술논문

Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.
Document Type
Academic Journal
Author
Hegde M; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA. mghegde@bcm.edu.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA. mghegde@bcm.edu.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. mghegde@bcm.edu.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. mghegde@bcm.edu.; Navai S; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; DeRenzo C; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.; Joseph SK; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Sanber K; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Medicine, Baylor College of Medicine, Houston, TX, USA.; Wu M; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Gad AZ; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.; Janeway KA; Department of Pediatrics, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Campbell M; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Mullikin D; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Nawas Z; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Robertson C; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Mathew PR; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Zhang H; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Mehta B; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Bhat RR; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Major A; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.; Shree A; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Gerken C; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Kalra M; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Chakraborty R; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Thakkar SG; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Dakhova O; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Salsman VS; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Grilley B; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Lapteva N; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.; Gee A; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dotti G; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Bao R; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; UPMC Hillman Cancer Center, Pittsburgh, PA, USA.; Salem AH; Department of Clinical Pharmacy, Ain Shams University, Cairo, Egypt.; Wang T; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Brenner MK; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Department of Medicine, Baylor College of Medicine, Houston, TX, USA.; Heslop HE; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Department of Medicine, Baylor College of Medicine, Houston, TX, USA.; Wels WS; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt, Germany.; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, Frankfurt, Germany.; Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany.; Hicks MJ; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.; Gottschalk S; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.; Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA.; Ahmed N; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA. nahmed@bcm.edu.; Center for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA. nahmed@bcm.edu.; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. nahmed@bcm.edu.; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. nahmed@bcm.edu.; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA. nahmed@bcm.edu.
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101761119 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2662-1347 (Electronic) Linking ISSN: 26621347 NLM ISO Abbreviation: Nat Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10 8 T cells per m 2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 10 8 CAR + T cells per m 2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 .
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)