Management of cytokine release syndrome: an update on emerging antigen-specific T cell engaging immunotherapies
Immunotherapy, 2019•Future Medicine
Antigen-specific immunotherapies have immense potential to harness and fortify the
inherent antitumor capacity of the immune system. Due to their unparalleled success in
recent years, antigen-targeting immunotherapies such as chimeric antigen receptor (CAR) T
cells [1, 2] and bi-specific T cell engagers (BiTEs)[2–5] have become state-ofthe-art
approaches for treating hematological malignancies. Although a significant portion of the
innovation and engineering has been invested toward improving the efficacy and potency of …
inherent antitumor capacity of the immune system. Due to their unparalleled success in
recent years, antigen-targeting immunotherapies such as chimeric antigen receptor (CAR) T
cells [1, 2] and bi-specific T cell engagers (BiTEs)[2–5] have become state-ofthe-art
approaches for treating hematological malignancies. Although a significant portion of the
innovation and engineering has been invested toward improving the efficacy and potency of …
Antigen-specific immunotherapies have immense potential to harness and fortify the inherent antitumor capacity of the immune system. Due to their unparalleled success in recent years, antigen-targeting immunotherapies such as chimeric antigen receptor (CAR) T cells [1, 2] and bi-specific T cell engagers (BiTEs)[2–5] have become state-ofthe-art approaches for treating hematological malignancies. Although a significant portion of the innovation and engineering has been invested toward improving the efficacy and potency of these T cell-engaging immunotherapies, these therapeutic strategies are prone to varying degrees of toxicities, including cytokine release syndrome (CRS) and neurotoxicity syndrome. For ensuring success of these promising and revolutionary therapies, both systematic grading and therapeutic management of CRS are essential for the field of immuno-oncology. In light of existing variability in assessment and management of toxicities across clinical centers, the American Society for Transplantation and Cellular Therapy (ASTCT) has released a consensus report for grading and management of CRS and neurotoxicity associated with immune effector cell therapies [6]. These consensus recommendations aim to standardize evaluation of therapeutic products employed in clinical trials across institutions. ASTCT has now defined CRS as a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells with symptoms that must include fever at the onset, and may include hypotension, capillary leak and end organ dysfunction [6]. This collaborative effort has been heralded as a step forward in management of toxicities. The purpose of this commentary is not recommendatory of specific strategies, nor does it demand revision on established consensus but rather provide an updated view on breakthroughs in CRS management (Figure 1) based on cytokine-targeting (IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-1β)[7–9] and engineering concepts (inhibitory CAR, CRISPR GM-CSFK/O)[2, 8] in both preclinical models and human studies. Herein, we will therefore address recent developments in the field of CRS management and limitations faced by current measures.
Future Medicine