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Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy.
Kaczanowska, Sabina; Murty, Tara; Alimadadi, Ahmad; Contreras, Cristina F; Duault, Caroline; Subrahmanyam, Priyanka B; Reynolds, Warren; Gutierrez, Norma A; Baskar, Reema; Wu, Catherine J; Michor, Franziska; Altreuter, Jennifer; Liu, Yang; Jhaveri, Aashna; Duong, Vandon; Anbunathan, Hima; Ong, Claire; Zhang, Hua; Moravec, Radim; Yu, Joyce; Biswas, Roshni; Van Nostrand, Stephen; Lindsay, James; Pichavant, Mina; Sotillo, Elena; Bernstein, Donna; Carbonell, Amanda; Derdak, Joanne; Klicka-Skeels, Jacquelyn; Segal, Julia E; Dombi, Eva; Harmon, Stephanie A; Turkbey, Baris; Sahaf, Bita; Bendall, Sean; Maecker, Holden; Highfill, Steven L; Stroncek, David; Glod, John; Merchant, Melinda; Hedrick, Catherine C; Mackall, Crystal L; Ramakrishna, Sneha; Kaplan, Rosandra N.
Afiliación
  • Kaczanowska S; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Murty T; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Alimadadi A; La Jolla Institute for Immunology, La Jolla, CA, USA; Immunology Center of Georgia, Augusta University, Augusta, GA, USA; Georgia Cancer Center, Medical College of Georgia at Augusta University, Augusta, GA, USA.
  • Contreras CF; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Oncology, University of Oxford, Oxford, UK.
  • Duault C; Stanford Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA, USA.
  • Subrahmanyam PB; Stanford Human Immune Monitoring Center, 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.
  • Gutierrez NA; La Jolla Institute for Immunology, La Jolla, CA, USA.
  • Baskar R; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Wu CJ; Broad Institute, Cambridge, MA, USA; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Michor F; Broad Institute, Cambridge, MA, USA.
  • Altreuter J; Broad Institute, Cambridge, MA, USA.
  • Liu Y; Broad Institute, Cambridge, MA, USA.
  • Jhaveri A; Broad Institute, Cambridge, MA, USA.
  • Duong V; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Anbunathan H; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Ong C; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Zhang H; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Moravec R; Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Yu J; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Biswas R; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Van Nostrand S; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Lindsay J; Dana-Farber Cancer Institute, Boston, MA, USA.
  • Pichavant M; Immunology Center of Georgia, Augusta University, Augusta, GA, USA.
  • Sotillo E; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Bernstein D; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Carbonell A; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Derdak J; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Klicka-Skeels J; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Segal JE; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Dombi E; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Harmon SA; Artificial Intelligence Resource, Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Turkbey B; Artificial Intelligence Resource, Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Sahaf B; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Bendall S; Georgia Cancer Center, Medical College of Georgia at Augusta University, Augusta, GA, USA.
  • Maecker H; Immunology Center of Georgia, Augusta University, Augusta, GA, USA.
  • Highfill SL; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
  • Stroncek D; Center for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, USA.
  • Glod J; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Merchant M; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Hedrick CC; La Jolla Institute for Immunology, La Jolla, CA, USA; Immunology Center of Georgia, Augusta University, Augusta, GA, USA; Georgia Cancer Center, Medical College of Georgia at Augusta University, Augusta, GA, USA.
  • Mackall CL; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Ramakrishna S; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: ramakrs@stanford.edu.
  • Kaplan RN; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: rosie.kaplan@nih.gov.
Cancer Cell ; 42(1): 35-51.e8, 2024 01 08.
Article en En | MEDLINE | ID: mdl-38134936
ABSTRACT
Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T cell assessments identified naive T cells in pre-treatment apheresis associated with good expansion, and exhausted T cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3+ monocytes in pre-treatment apheresis associated with good expansion. Longitudinal analysis of post-treatment samples identified increased CXCR3- classical monocytes in all groups as CAR-T numbers waned. Together, our data uncover mediators of CAR-T biology and correlates of expansion that could be utilized to advance immunotherapies for solid tumor patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Quiméricos de Antígenos / Neuroblastoma Límite: Adult / Child / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Quiméricos de Antígenos / Neuroblastoma Límite: Adult / Child / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos