Focused evaluation of the roles of macrophages in chimeric antigen receptor (CAR) T cell therapy associated cytokine release syndrome

Abstract

Cytokine release syndrome (CRS) is a major obstacle to the widespread clinical application of chimeric antigen receptor (CAR) T cell therapies. CRS can also be induced by infections (such as SARS-CoV-2), drugs (such as therapeutic antibodies), and some autoimmune diseases. Myeloid-derived macrophages play key roles in the pathogenesis of CRS, and participate in the production and release of the core CRS cytokines, including interleukin (IL)-1, IL-6, and interferon-γ. In this review, we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.

An integrated microfluidics platform with high-throughput single-cell cloning array and concentration gradient generator for efficient cancer drug effect screening

“…Though we only demonstrated the application of screening anticancer drug effect by using the “SMART” microfluidic platform, we anticipate its wide use in single-cell based analysis. For example, it could be harnessed to profile the cytolytic activity of single T cells against the target cells in immunotherapy [ 9 , 42 ], since our device allows great control and efficient tracking of small primary cells. Furthermore, it is possible to extract the cells of interest for downstream analysis (e.g., single cell sequence) if combining some automatic instruments such as laser capture microdissection systems.…”

Hematopoiesis and immune reconstitution after CD19 directed chimeric antigen receptor T‐cells (CAR‐T): A comprehensive review on incidence, risk factors and current management

“…Overall, the role of inflammatory cytokines in the development of post‐CAR T‐cell cytopenias may result controversial. Tumor antigen recognition by engineered CARs leads to T‐cell activation and proliferation, resulting in macrophage activation and release of cytokines such as IFN‐γ, IL‐2R, IL‐6, IL‐10, IL‐12, IL‐18, IL‐1β, TNF‐α, IL‐33, and ferritin 26,27 . High levels of IFN‐γ can trigger myelosuppression through induction of stem cell exhaustion by hematopoiesis stress, and stem cell niche damage 28 .…”

A Bibliometric and Knowledge-Map Analysis of CAR-T Cells From 2009 to 2021

“…From these keywords, we can summarize the general situation of CAR-T cell-related fields, including a. CAR-T cell therapy, which is antitumor immunotherapy; b. The activation of CAR-T cells and the expression of CARs are important factors for the function of CAR-T cells; c. CRS is a common and most studied adverse reaction of CAR-T cell therapy (78,79); d. CAR-T cell therapy is widely used in the research and treatment of hematological malignancies (80,81); e. Presently, most clinical trials related to CAR-T cells are in phase-I (can be verified in clinicaltrials.gov); f. Anti-tumor activity and efficacy are the research emphases in this field (82,83); g. CD19 is the most commonly used target in treating hematological malignancies (80,84); h. CAR-NK cell therapy is currently a research hotspot (85,86).…”

“…The high-quality and high-impact research related to CAR-T cells mainly focuses on the clinical experimental studies of CD19-CAR-T cells in hematological malignancies. Related research hotspots include efficacy, safety, drug resistance, and the mechanism and management of related toxic reactions (50,51,56,70,90,91); b. CRS is a common and most studied CAR-T cell-related toxic reaction (78,79). Related studies mainly focus on the mechanism, diagnosis (biomarkers), and intervention (especially related therapeutic drug "anakinra") of CRS (92,93,97); c. CD19 is the most commonly used target of CAR-T cells in treating hematological malignancies (80,84).…”