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Possible Compartmental Cytokine Release Syndrome in a Patient With Recurrent Ovarian Cancer After Treatment With Mesothelin-targeted CAR-T Cells

Tanyi, Janos L.; Stashwick, Caitlin; Plesa, Gabriela; Morgan, Mark A.; Porter, David; Maus, Marcela V.; June, Carl H.

doi: 10.1097/CJI.0000000000000160
Clinical Studies
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Cytokine release syndrome (CRS) is a potentially severe systemic toxicity seen after adoptive T-cell therapy and caused by T-cell activation and proliferation and is associated with elevated circulating levels of cytokines such as C-reactive protein, interleukin-6 (IL-6), and interferon-γ and has previously been described as a systemic response in hematologic malignancies. A 52-year-old woman with BRCA 1 mutation positive heavily pretreated advanced recurrent serous ovarian cancer was treated under a compassionate use protocol with autologous mesothelin-redirected chimeric antigen receptor T cells (CART-meso). Autologous T cells were transduced to express a receptor composed of an extracellular antimesothelin single-chain variable fragment fused to 4-1BB and TCR-zeta signaling domain. This patient was infused with 3×107 CART-meso T cells/m2 without lymphodepletion and developed compartmental CRS confined to the pleural cavities. The compartmental CRS was evidenced by an increase in IL-6 and accumulation of CART-meso T cells in pleural fluid compared with peripheral blood and was successfully treated the anti-IL6 receptor antagonist tocilizumab on D21 after the T-cell infusion. This is the first description of a compartmental CRS in a patient with solid malignancy. This response could be due to malignant pleural fluid creating an environment where T cells could interact with tumor cells and suggests localized on-target CAR-T-cell activation.

*Department of Obstetrics and Gynecology

Department of Pathology and Laboratory Medicine, Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia

Department of Obstetrics and Gynecology, Lancaster General Health/Penn Medicine, Lancaster, PA

§Department of Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA

Reprints: Janos L. Tanyi, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104. E-mail: janos.tanyi@uphs.upenn.edu.

Received January 21, 2016

Accepted January 23, 2017

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