Abstract S04-02: Treatment with tocilizumab does not inhibit induction of anti-COVID-19 antibodies in patients with severe SARS-CoV-2 infection
Authors: Cabanov Alexandra , Flood Blake A. , Bloodworth Jeffrey , Higgs Emily F. , Fessler Jessica , Leung Michael Y.K. , Cron Kyle R. , Trujillo Jonathan , Pyzer Athalia R. , Rouhani Sherin , Strohbehn Garth , Heiss Brian , Ratain Mark , Reid Pankti , Yeo Kiang-Teck J. , Sweis Randy F. , Zha Yuanyuan , Gajewski Thomas F. 
Published: December 2020

Abstract
Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor-blocking monoclonal antibody, is used to treat various rheumatologic conditions and cytokine release syndrome in CAR-T cell therapy and has been repurposed to treat COVID-19-related hyperinflammation. There are limited data available reporting how TCZ affects the immune response in the context of COVID-19. To investigate this question, we recruited patients treated with TCZ as part of a COVID-19 biobanking protocol (A-28063295) to study immune parameters that might be affected. We enrolled 19 patients who were treated with a range of 40-200mg TCZ as part of a low-dose TCZ trial (COVIDOSE, reported separately as abstract A-94803796), and 11 patients who received 400mg TCZ on a standard-of-care expanded-access basis. As IL-6 acts as a stimulant of B-cell proliferation, plasma cell maturation, and antibody responses, we evaluated whether blocking the IL-6 receptor with TCZ therapy impairs antibody generation to SARS-CoV-2. To evaluate antibody levels in these patients, we performed ELISAs against the SARS-CoV-2 spike glycoprotein and its receptor-binding domain (RBD). The spike glycoprotein, a structural protein of SARS-CoV-2, is a crucial component in the recognition, attachment, and entry of the virus into host cells. Specifically, the RBD is responsible for binding the ACE2 receptor on human cells, and likely serves as a major target for neutralizing antibodies. To establish if the formation and persistence of antibodies was affected by TCZ treatment, we analyzed serum and plasma samples longitudinally from 29 patients treated with TCZ and 26 control patients. To account for potential variability between plates, the measured optical density (OD) values were normalized to the OD for COVID-19-negative control serum at 1:50 dilution, and the same negative control was tested on each plate. Titers were calculated as the linear interpolation of the inverse dilution at which the normalized OD value crossed a threshold of 1, representing the maximum OD measured for the negative control. Anti-spike and anti-RBD antibodies increased significantly over time in both TCZ-treated patients and controls (p &lt; 0.005 for both). Increasing antibody titers throughout the disease course followed a similar trajectory in TCZ-treated patients compared to control patients, suggesting that TCZ treatment does not impede the generation of antibodies to SARS-CoV-2. Additionally, TCZ-treated patients achieved comparable maximal observed antibody titers to control patients (average maximal log10 (titer) of 5.42 and 4.96 for spike and of 4.39 and 4.44 for RBD, respectively). These data suggest that TCZ does not impair the induction of anti-SARS-CoV-2 antibodies.
Citation Format: Alexandra Cabanov, Blake A. Flood, Jeffrey Bloodworth, Emily F. Higgs, Jessica Fessler, Michael Y.K. Leung, Kyle R. Cron, Jonathan Trujillo, Athalia R. Pyzer, Sherin Rouhani, Garth Strohbehn, Brian Heiss, Mark Ratain, Pankti Reid, Kiang-Teck J. Yeo, Randy F. Sweis, Yuanyuan Zha, Thomas F. Gajewski. Treatment with tocilizumab does not inhibit induction of anti-COVID-19 antibodies in patients with severe SARS-CoV-2 infection [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S04-02.