RT Journal Article
SR Electronic
T1 Tocilizumab, but not dexamethasone, prevents CRS without affecting antitumor activity of bispecific antibodies
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000621
DO 10.1136/jitc-2020-000621
VO 8
IS 1
A1 Kauer, Joseph
A1 Hörner, Sebastian
A1 Osburg, Lukas
A1 Müller, Stefanie
A1 Märklin, Melanie
A1 Heitmann, Jonas S
A1 Zekri, Latifa
A1 Rammensee, Hans-Georg
A1 Salih, Helmut R
A1 Jung, Gundram
YR 2020
UL http://jitc.bmj.com/content/8/1/e000621.abstract
AB 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.