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

• Published in: Nature communications Vol. 11; no. 1; p. 3549
• Main Authors: Hegde, Meenakshi, Joseph, Sujith K., Pashankar, Farzana, DeRenzo, Christopher, Sanber, Khaled, Navai, Shoba, Byrd, Tiara T., Hicks, John, Xu, Mina L., Gerken, Claudia, Kalra, Mamta, Robertson, Catherine, Zhang, Huimin, Shree, Ankita, Mehta, Birju, Dakhova, Olga, Salsman, Vita S., Grilley, Bambi, Gee, Adrian, Dotti, Gianpietro, Heslop, Helen E., Brenner, Malcolm K., Wels, Winfried S., Gottschalk, Stephen, Ahmed, Nabil
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.07.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/106; 13/21; 13/31; 13/51; 631/250; 631/67; 692/4028; 692/4028/67/1798; 82/81; Autoantibodies; Autografts; Biopsy; Bone marrow; Bone Marrow - pathology; Chemotherapy; Child; Children; Clinical Trials, Phase I as Topic; ErbB-2 protein; Humanities and Social Sciences; Humans; Immunotherapy, Adoptive - methods; Lymphocytes; Lymphocytes T; Male; Metastases; Metastasis; Monoclonal antibodies; multidisciplinary; Muscle Neoplasms - immunology; Muscle Neoplasms - pathology; Muscle Neoplasms - therapy; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - therapy; Pembrolizumab; Receptor, ErbB-2 - immunology; Receptors, Chimeric Antigen - immunology; Remission; Remission Induction - methods; Rhabdomyosarcoma; Rhabdomyosarcoma - immunology; Rhabdomyosarcoma - secondary; Rhabdomyosarcoma - therapy; Science; Science (multidisciplinary); Signal transduction; T cell receptors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - transplantation; Transplantation, Autologous - methods; Treatment Outcome
• ISSN: 2041-1723; 2041-1723
• 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. Recurrent metastatic rhabdomyosarcoma remains largely incurable. Here, the authors describe a child with metastatic rhabdomyosarcoma who has durable response to HER2-specific CAR T cells and shows endogenous immune reactivity.