TY - JOUR
T1 - Systemic inflammatory response syndrome after administration of unmodified T lymphocytes
AU - Papadopoulou, Anastasia
AU - Krance, Robert A.
AU - Allen, Carl E.
AU - Lee, Daniel Y.
AU - Rooney, Cliona M.
AU - Brenner, Malcolm
AU - Leen, Ann M.
AU - Heslop, Helen
N1 - Funding Information:
We are grateful to Amy Reyna—the study coordinator, Deborah Lyon for quality control testing, April Durett for phenotypic analyses, and Oumar Diouf for assistance with good manufacturing practice production. H.E.H. is supported by a Dan L Duncan Chair and M.K.B. is supported by a Fayez Sarofim Chair. The parent clinical trial was supported in part by the Production Assistance for Cellular Therapies (PACT) program [National Heart, Lung, and Blood Institute contract #HHSN268201000007C], Alex’s Lemonade Stand Foundation, the Clinical Research Center at Texas Children’s Hospital, and the Dan L. Duncan Institute for Clinical and Translational Research at Baylor College of Medicine. We also appreciate the support of resources shared by Dan L Duncan Cancer Center through support grant P30CA125123.
PY - 2014/6
Y1 - 2014/6
N2 - 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.
AB - 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.
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U2 - 10.1038/mt.2014.48
DO - 10.1038/mt.2014.48
M3 - Article
C2 - 24651135
AN - SCOPUS:84902158704
VL - 22
SP - 1134
EP - 1138
JO - Molecular therapy : the journal of the American Society of Gene Therapy
JF - Molecular therapy : the journal of the American Society of Gene Therapy
SN - 1525-0016
IS - 6
ER -