Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma
Open Access
- 15 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-15
- https://doi.org/10.1038/s41467-020-17175-8
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.Keywords
Funding Information
- EIF | Stand Up To Cancer (SU2C-AACR-DT1113)
- American Association for Cancer Research (SU2C-AACR-DT1113)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (1U54CA232568-01, K12CA090433)
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Cancer Prevention and Research Institute of Texas (RP101335, RP160283)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute
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