Systemic Inflammatory Response Syndrome After Administration of Unmodified T Lymphocytes

• Published in: Molecular therapy Vol. 22; no. 6; pp. 1134 - 1138
• Main Authors: Papadopoulou, Anastasia, Krance, Robert A, Allen, Carl E, Lee, Daniel, Rooney, Cliona M, Brenner, Malcolm K, Leen, Ann M, Heslop, Helen E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2014; Elsevier Limited; Nature Publishing Group
• Subjects: Adenoviruses; Anti-Inflammatory Agents - therapeutic use; Antibodies; Antigens; Biopsy; Cardiac arrhythmia; Cells; Cytokines; Cytokines - metabolism; Dehydrogenases; Drug dosages; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens - immunology; Etanercept; Fever; Gene therapy; Herpesvirus 4, Human - immunology; Hodgkin Disease - immunology; Hodgkin Disease - therapy; Hodgkin Disease - virology; Humans; Hypotension; Immunoglobulin G - therapeutic use; Immunotherapy - adverse effects; Lymphocytes; Lymphoma; Medicine; Original; Patients; Physiology; Prednisone - therapeutic use; Receptors, Tumor Necrosis Factor - therapeutic use; Steroids; Systemic Inflammatory Response Syndrome - complications; Systemic Inflammatory Response Syndrome - drug therapy; Systemic Inflammatory Response Syndrome - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - transplantation; Tomography; Tumor necrosis factor-TNF; Young Adult; United States > US; Texas
• ISSN: 1525-0016; 1525-0024; 1525-0024
• DOI: 10.1038/mt.2014.48

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.