Tocilizumab, but not dexamethasone, prevents CRS without affecting antitumor activity of bispecific antibodies. Issue 1 (30th May 2020)

• Record Type: Journal Article
• Authors: Kauer, Joseph; Hörner, Sebastian; Osburg, Lukas; Müller, Stefanie; Märklin, Melanie; Heitmann, Jonas S; Zekri, Latifa; Rammensee, Hans-Georg; Salih, Helmut R; Jung, Gundram
• Is Part Of: Journal for immunotherapy of cancer. Volume 8:Issue 1(2020)
• Publication Date: 2020-05-30
• Subjects: immunotherapy -- antibodies, neoplasm -- lymphocyte activation; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-000621
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Bispecific antibodies (bsAb) and chimeric antigen receptor (CAR) T cells allow for antibody guided recruitment of T cells against tumors. Both are successfully used for treatment of CD19 expressing leukemias, but may cause cytokine release syndrome (CRS) as a major dose-limiting side effect. For CRS prevention, steroids are recommended prior to bsAb treatment, despite their well-known lymphotoxic activity. The IL-6 receptor antibody tocilizumab is established for treatment of CRS induced by CAR T cells, but was not considered for CRS prevention in bsAb therapy. We here compared the influence of dexamethasone and tocilizumab on bsAb-mediated T cell proliferation and tumor lysis in vitro and in vivo and found that dexamethasone profoundly inhibited T cell proliferation and antitumor activity as induced by two different bsAb, particularly at low effector:target ratios, whereas tocilizumab did not affect efficacy. When we applied tocilizumab early during treatment of three patients with a newly developed PSMAxCD3 bsAb, significant CRS attenuation despite high IL-6 serum levels was observed. Thus, early IL-6 blockade may reduce the undesired sequelae of CRS upon bsAb therapy without affecting therapeutic activity, allowing in turn for safe application of effective doses.