@article{ad9ff04a068348fa9e83842f785979d7,
title = "Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma",
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.",
author = "Meenakshi Hegde and Joseph, {Sujith K.} and Farzana Pashankar and Christopher DeRenzo and Khaled Sanber and Shoba Navai and Byrd, {Tiara T.} and John Hicks and Xu, {Mina L.} and Claudia Gerken and Mamta Kalra and Catherine Robertson and Huimin Zhang and Ankita Shree and Birju Mehta and Olga Dakhova and Salsman, {Vita S.} and Bambi Grilley and Adrian Gee and Gianpietro Dotti and Helen Heslop and Brenner, {Malcolm K.} and Wels, {Winfried S.} and Stephen Gottschalk and Nabil Ahmed",
note = "Funding Information: We thank the patient and his family as well as the physicians and nursing staff involved in this child{\textquoteright}s care. The trial was supported by Stand Up To Cancer (SU2C)— St. Baldrick{\textquoteright}s Pediatric Cancer Dream Team Translational Research Grant (SU2C-AACR-DT1113); SU2C is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research (AACR). This work was also supported by Alex{\textquoteright}s Lemonade Stand Pediatric Cancer Foundation, Cancer Prevention Research Institute of Texas (CPRIT) grant (RP101335), The V Foundation for Cancer Research, Triumph Over Kid Cancer Foundation, and Cookies for Kids{\textquoteright} CancerTM Foundation. Further support was provided by the Clinical Research Center at Texas Children{\textquoteright}s Hospital and by shared resources through Dan L. Duncan Cancer Center Support Grant P30CA125123. M.H., S.K.J., K.S., and N.A. were supported by the National Cancer Institute of the National Institute for Health under the Cancer Moonshot U54 project 1U54CA232568-01. K.S. was supported by the State of Texas CPRIT training program RP160283—Baylor College of Medicine Comprehensive Cancer Training Program. S.N. was supported by the National Cancer Institute of the National Institutes for Health under award number K12CA090433. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: M.H., S.K.J., T.T.B., and V.S.S. are named inventors on patent applications in the field of CAR T-cell therapy owned by Baylor College of Medicine (BCM). B.G. owns QBRegulatory Consultants, LLC (QBR) which provides clinical research regulatory and project management support to companies inclusive of Allovir, TESSA therapeutics, Marker Therapeutics Inc, and LOKON Pharma AB. H.E.H. reports ownership equity in Marker Therapeutics and Allovir, consulting with Tessa Therapeutics, Kiadis, Novartis, Gilead Biosciences, PACT Pharma, Marker Therapeutics, and Allovir, and research grants from Tessa Therapeutics and Cell Medica, outside the submitted work. M.K.B. reports ownership equity in Marker Therapeutics, Tessa Therapeutics, and Allovir, consulting with Tessa Therapeutics, Walking Fish Therapeutic, Memgen, TScan, Allogene, Marker Therapeutics, and Allovir, outside the submitted work. W.S.W. is named as an inventor on patents and patent applications in the field of cancer immunotherapy owned by Georg-Speyer-Haus. S.G. has patent applications in the fields of T-cell and/or gene therapy for cancer and a research collaboration with TESSA Therapeutics, is a DSMB member of Immatics, and on the scientific advisory board of Tidal. N.A. is named inventor on patents and patent applications owned by Baylor College of Medicine. N.A. received one-time royalties from Celgene and Cell Medica, consulted in the past for Adaptimmune and continues to consult for Equillium (pro bono) and The Children{\textquoteright}s Cancer Hospital Egypt 57357 on medical education and research development. None of these relationships conflict with the published work. The remaining authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = jul,
day = "15",
doi = "10.1038/s41467-020-17175-8",
language = "English (US)",
volume = "11",
journal = "Nat Commun",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}