Systemic inflammatory response syndrome after administration of unmodified T lymphocytes

Anastasia Papadopoulou, Robert A. Krance, Carl E. Allen, Daniel Y. Lee, Cliona M. Rooney, Malcolm Brenner, Ann M. Leen, Helen Heslop

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Systemic inflammatory response syndrome (SIRS) is a rare systemic inflammatory response associated with fever, tachycardia, profound hypotension, and respiratory distress, which has been reported in cancer patients receiving T cells genetically modified with chimeric antigen receptors to retarget their specificity to tumor-associated antigens. The syndrome usually occurs following significant in vivo expansion of the infused cells and has been associated with tumor destruction/lysis. Analysis of patient plasma has shown elevated cytokine levels, and resolution of symptoms has been reported after administration of steroids and/or antibodies (such as anti-tumor necrosis factor and anti-interleukin (IL)-6 receptor antibodies) that interfere with cytokine responses.To date, SIRS has not been reported in subjects receiving genetically unmodified T cells with native receptors directed against tumor antigens, in which greater physiological control of T-cell activation and expansion may occur. Here, however, we report a patient with bulky refractory Epstein-Barr virus (EBV)-associated lymphoma, who developed this syndrome 2 weeks after receiving T cells directed against EBV antigens through their native receptors. She was treated with steroids and etanercept, with rapid resolution of symptoms. SIRS may therefore occur even when T cells recognize antigens physiologically through their "wild-type" native receptors and should be acknowledged as a potential complication of this therapy.

Original languageEnglish (US)
Pages (from-to)1134-1138
Number of pages5
JournalMolecular Therapy
Volume22
Issue number6
DOIs
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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