Systemic inflammatory response syndrome after administration of unmodified T lymphocytes

Mol Ther. 2014 Jun;22(6):1134-1138. doi: 10.1038/mt.2014.48. Epub 2014 Mar 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Cytokines / metabolism
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • Etanercept
  • Herpesvirus 4, Human / immunology
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / therapy
  • Hodgkin Disease / virology
  • Humans
  • Immunoglobulin G / therapeutic use
  • Immunotherapy / adverse effects
  • Prednisone / therapeutic use
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Systemic Inflammatory Response Syndrome / complications
  • Systemic Inflammatory Response Syndrome / drug therapy*
  • Systemic Inflammatory Response Syndrome / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / transplantation*
  • Young Adult


  • Anti-Inflammatory Agents
  • Cytokines
  • Epstein-Barr Virus Nuclear Antigens
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Etanercept
  • Prednisone