Immunomodulatory Therapeutic Proteins in COVID‐19: Current Clinical Development and Clinical Pharmacology Considerations

Abstract

The coronavirus disease 2019 (COVID‐19) pandemic caused by infection with SARS‐CoV‐2 has led to more than 600 000 deaths worldwide. Patients with severe disease often experience acute respiratory distress characterized by upregulation of multiple cytokines. Immunomodulatory biological therapies are being evaluated in clinical trials for the management of the systemic inflammatory response and pulmonary complications in patients with advanced stages of COVID‐19. In this review, we summarize the clinical pharmacology considerations in the development of immunomodulatory therapeutic proteins for mitigating the heightened inflammatory response identified in COVID‐19.

Intrinsic differences in the mechanisms of Tie2 binding to angiopoietins exploited by directed evolution to create an Ang2-selective ligand trap

“…Blocking Ang2 action with neutralizing antibodies has been shown to suppress Ang2mediated vascular effects and improve outcomes in preclinical models of a range of diseases, including sepsis, acute and chronic myocardial damage following infarction and inflammatory lung disease [19][20][21] . Consequently, several monoclonal antibodies that block Ang2 are currently in clinical trials for conditions from acute respiratory distress syndrome induced by Covid-19 to diabetic eye disease 7,8 . In addition to antibodies, ligand-traps have been successful in blocking effects of ligands whose elevated expression contribute to disease 9 .…”

“…There is considerable interest in developing inhibitors of Ang2 for therapeutic use. A number of monoclonal antibodies selectively binding Ang2 are in clinical trials for diseases ranging from Covid-19-induced acute respiratory distress to diabetic eye disease 7,8 . An alternative and complementary approach to antibodies for blocking pathological effects of ligands is the ligand-trap 9 .…”

Integrating heterogeneous data to facilitate COVID-19 drug repurposing

“…Some studies suggest the use of immunotherapy to treat the heightened inflammatory response and the pulmonary complications that SARS-CoV-2 produces in some patients. [14] , [15] IL2 can be a suitable immunomodulator for improving the state of COVID-19 patients as it induces the proliferation and maturation of cells (regulatory T cells) that play a role in the control of excessive inflammation. [15] There is currently a clinical trial that aims to demonstrate the efficacy of low-dose IL2 in COVID-19 patients who develop acute respiratory distress syndrome.…”

Recent advances in antibody‐based immunotherapy strategies for COVID‐19

“…This antibody is used to treat unresectable pancreatic cancer and is currently in phase II of the COVID‐19 clinical trial. 184 , 185 …”