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

Nature Communications
Meenakshi HegdeNabil Ahmed

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.

Associated Clinical Trials

References

Nov 24, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R GorlickP A Meyers
Jun 5, 2003·European Journal of Immunology·Maureen M HughesBarry P Sleckman
Apr 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark E DudleySteven A Rosenberg
Feb 3, 2007·The Journal of Clinical Investigation·Claudia WrzesinskiNicholas P Restifo
May 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Odile OberlinJames R Anderson
Sep 24, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark E DudleySteven A Rosenberg
Jun 18, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Nabil AhmedStephen Gottschalk
Sep 22, 2010·Cancer Immunology, Immunotherapy : CII·Franz Josef GassnerInge Tinhofer
Mar 27, 2013·The New England Journal of Medicine·Stephan A GruppCarl H June
Aug 7, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jane RenshawJanet Shipley
Aug 14, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Meenakshi HegdeNabil Ahmed
Oct 26, 2013·Nature Communications·Christopher S CarlsonHarlan Robins
Mar 20, 2014·Nature Reviews. Clinical Oncology·Mark LinchCharlotte Benson
Feb 5, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Debraj GuhaThakurtaCharles G Drake
Mar 25, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nabil AhmedStephen Gottschalk
Apr 4, 2015·Science·Ton N Schumacher, Robert D Schreiber
Jul 19, 2016·The Journal of Clinical Investigation·Meenakshi HegdeNabil Ahmed
Mar 16, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James N KochenderferSteven A Rosenberg
Apr 5, 2017·Journal of the National Cancer Institute·James L GulleyCharles G Drake
Apr 22, 2017·Cell·Brendan D Manning, Alex Toker
Jun 14, 2017·Cancer Cell·Praveen AgrawalEva Hernando
Dec 9, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alberto S Pappo, Uta Dirksen
Feb 1, 2018·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Mar 1, 2018·Cell Reports·Yin ZhaoBo Zhong
Jun 1, 2018·Nature·Joseph A FraiettaJ Joseph Melenhorst
Jun 15, 2018·BMC Cancer·Giulia BertoliniPatrizia Gasparini
Jan 12, 2019·Nature Reviews. Immunology·Christine E Brown, Crystal L Mackall
Feb 27, 2020·Pediatric Blood & Cancer·Kayleen A Bailey, Leonard H Wexler

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Citations

Sep 15, 2020·Current Opinion in Hematology·Ofrat Beyar-Katz, Saar Gill
Nov 28, 2020·Expert Opinion on Biological Therapy·Natasha Bechman, John Maher
Feb 12, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mary K McKennaMalcolm K Brenner
Feb 27, 2021·Nature Reviews. Clinical Oncology·Dimitrios L WagnerMohamed Abou-El-Enein
Mar 19, 2021·PloS One·Christine AmbrosePaul D Rennert
Apr 21, 2021·Journal of Hematology & Oncology·Julien EdelineMarion Alcantara
Aug 10, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Fan TangXia-Wei Wei
Aug 11, 2021·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D MeyranP J Neeson
Jul 27, 2021·Current Opinion in Oncology·Nuria KoteckiAhmad Awada
Aug 21, 2021·The Journal of Experimental Medicine·Chuan YanDavid M Langenau
Aug 22, 2021·Genes, Chromosomes & Cancer·Shamik MitraFredrik Mertens
Oct 10, 2021·Advanced Healthcare Materials·Zhaoyu MaHeyou Han
Sep 27, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jessica WagnerStephen Gottschalk

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Methods Mentioned

BETA
bone
biopsy
flow cytometry
bone marrow aspiration
ELISA
biopsies
lymphodepletion
Assay
PCR
antibody

Clinical Trials Mentioned

NCT00902044

Software Mentioned

Cytoscape
[UNK] Prospector
ImmunoSEQ Analyzer
GraphPad Prism
GenePix
ProtoArray ® Prospector
Excel
FlowJo

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