Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma

Nat Commun. 2020 Jul 15;11(1):3549. doi: 10.1038/s41467-020-17175-8.


Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biopsy
  • Bone Marrow / pathology
  • Child
  • Clinical Trials, Phase I as Topic
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Male
  • Muscle Neoplasms / immunology
  • Muscle Neoplasms / pathology
  • Muscle Neoplasms / therapy*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / therapy*
  • Receptor, ErbB-2 / immunology*
  • Receptors, Chimeric Antigen / immunology
  • Remission Induction / methods
  • Rhabdomyosarcoma / immunology
  • Rhabdomyosarcoma / secondary
  • Rhabdomyosarcoma / therapy*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*
  • Transplantation, Autologous / methods
  • Treatment Outcome


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

Associated data

  • ClinicalTrials.gov/NCT00902044