Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial

Nat Cancer. 2024 Jun;5(6):880-894. doi: 10.1038/s43018-024-00749-6. Epub 2024 Apr 24.


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 × 108 T cells per m2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 108 CAR+ T cells per m2 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. registration: NCT00902044 .

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Female
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Lymphocyte Depletion / methods
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptor, ErbB-2*
  • Receptors, Chimeric Antigen* / immunology
  • Sarcoma* / immunology
  • Sarcoma* / therapy
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use


  • Receptor, ErbB-2
  • ERBB2 protein, human
  • Receptors, Chimeric Antigen
  • fludarabine
  • Vidarabine
  • Cyclophosphamide

Associated data