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Bioactivity and safety of chimeric switch receptor T cells in glioblastoma patients.

Abstract
Experimental evidence has shown that chimeric switch receptor T (CSR-T) cells, activated by binding programmed death-ligand 1 on the tumor cell surface, lead to tumor regression in experimental animals. In this phase I clinical study, we evaluated the safety and bioactivity of CSR-T cell therapy in 14 patients with recurrent glioblastoma who were unresponsive to surgical resection and standard radiotherapy. Patients who received 108 CSR-T cells either intravenously or intracranially showed an increase in the levels of IFN-gamma and IL-6, respectively, in peripheral blood or cerbrospinal fluid (CSF). Moreover, the number of T cells present in CSF significantly increased after the treatment. Patients did not show grade 3 or 4 adverse effects. The evidence of in vivo biological activity and lack of adverse effects of treatment with CSR-T cells suggest that such treatment can be subjected to further analysis to show the efficacy of this new treatment strategy in the treatment of cancers that are not responsive to traditional therapeutic regimens.
AuthorsJun-Xiu Guo, Chen-Xing Wu, Peng-Fei Wang, Zhong-Jun Li, Song Han, Wen Jin, Zhi-Xiong Lin
JournalFrontiers in bioscience (Landmark edition) (Front Biosci (Landmark Ed)) Vol. 24 Issue 6 Pg. 1158-1166 (06 01 2019) ISSN: 2768-6698 [Electronic] Singapore
PMID31136972 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-6
  • Receptors, Chimeric Antigen
  • Interferon-gamma
Topics
  • Adult
  • Aged
  • Brain Neoplasms (immunology, pathology, therapy)
  • Female
  • Glioblastoma (immunology, pathology, therapy)
  • Humans
  • Immunotherapy, Adoptive (methods)
  • Interferon-gamma (blood, cerebrospinal fluid, immunology)
  • Interleukin-6 (blood, cerebrospinal fluid, immunology)
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Receptors, Chimeric Antigen (immunology, metabolism)
  • Treatment Outcome

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