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 Dotti, Helen E. Heslop, Malcolm K. Brenner, Winfried S. Wels, Stephen Gottschalk and Nabil Ahmed ()
Additional contact information
Meenakshi Hegde: Baylor College of Medicine
Sujith K. Joseph: Baylor College of Medicine
Farzana Pashankar: Yale University School of Medicine
Christopher DeRenzo: Baylor College of Medicine
Khaled Sanber: Baylor College of Medicine
Shoba Navai: Baylor College of Medicine
Tiara T. Byrd: Baylor College of Medicine
John Hicks: Baylor College of Medicine
Mina L. Xu: Yale University School of Medicine
Claudia Gerken: Baylor College of Medicine
Mamta Kalra: Baylor College of Medicine
Catherine Robertson: Baylor College of Medicine
Huimin Zhang: Baylor College of Medicine
Ankita Shree: Baylor College of Medicine
Birju Mehta: Baylor College of Medicine
Olga Dakhova: Baylor College of Medicine
Vita S. Salsman: Baylor College of Medicine
Bambi Grilley: Baylor College of Medicine
Adrian Gee: Baylor College of Medicine
Gianpietro Dotti: Department of Microbiology and Immunology at University of North Carolina
Helen E. Heslop: Baylor College of Medicine
Malcolm K. Brenner: Baylor College of Medicine
Winfried S. Wels: Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy
Stephen Gottschalk: Baylor College of Medicine
Nabil Ahmed: Baylor College of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-17175-8

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