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

Meenakshi Hegde, Sujith K. Joseph, Farzana Pashankar, Christopher DeRenzo, Khaled Sanber, Shoba Navai, Tiara T. Byrd, John Hicks, Mina L. Xu, Claudia Gerken, Mamta Kalra, Catherine Robertson, Huimin Zhang, Ankita Shree, Birju Mehta, Olga Dakhova, Vita S. Salsman, Bambi Grilley, Adrian Gee, Gianpietro DottiHelen Heslop, Malcolm K. Brenner, Winfried S. Wels, Stephen Gottschalk, Nabil Ahmed

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number3549
JournalNature Communications
Volume11
Issue number1
DOIs
StatePublished - Jul 15 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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