AUTHOR=Haroun Grace , Gordon Erlinda M. TITLE=DeltaRex-G, tumor targeted retrovector encoding a CCNG1 inhibitor, for CAR-T cell therapy induced cytokine release syndrome JOURNAL=Frontiers in Molecular Medicine VOLUME=4 YEAR=2024 URL=https://www.frontiersin.org/journals/molecular-medicine/articles/10.3389/fmmed.2024.1461151 DOI=10.3389/fmmed.2024.1461151 ISSN=2674-0095 ABSTRACT=

Cytokine release syndrome is a serious complication of chimeric antigen receptor-T cell therapy and is triggered by excessive secretion of inflammatory cytokines by chimeric T cells which could be fatal. Following an inquiry into the molecular mechanisms orchestrating cytokine release syndrome, we hypothesize that DeltaRex-G, a tumor targeted retrovector encoding a cytocidal CCNG1 inhibitor gene, may be a viable treatment option for corticosteroid-resistant cytokine release syndrome. DeltaRex-G received United States Food and Drug Administration Emergency Use Authorization to treat Covid-19-induced acute respiratory distress syndrome, which is due to hyperactivated immune cells. A brief administration of DeltaRex-G would inhibit a certain proportion of hyperactive chimeric T cells, consequently reducing cytokine release while retaining chimeric T cell efficacy.