Dataset Information

IL-6/IFN-γ double knockdown CAR-T cells reduce the release of multiple cytokines from PBMCs in vitro.

ABSTRACT: CD19-targeted chimeric antigen receptor T (anti-CD19 CAR-T) cells have shown good therapeutic results in the treatment of CD19 + B cell acute lymphocytic leukemia and lymphoma. However, severe side reactions and cytotoxicity are great challenges in the application of anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) is the main side effect of CAR-T cell treatment, and interleukin-6 (IL-6) and interferon γ (IFN-γ) are cytokines that play major roles in CRS. Therefore, we investigated double knockdown (KD) of IL-6 and IFN-γ as a potential strategy to manage anti-CD19 CAR-T cell-associated CRS. These improved anti-CD19 CAR-T cells therapy retained the advantages of the original anti-CD19 CAR-T cells and additionally reduced the release of cytokines from CAR-T cells and other immune cells. Moreover, this study presented a novel approach to abrogate CRS through IL-6 and IFN-γ KD, which may potentially inhibit the release of multiple cytokines from CAR-T cells and peripheral blood mononuclear cells (PBMCs), a model of CRS correlate with in vivo features of the CAR-T therapy, thereby reducing the impact of CRS, improving the safety of CAR-T cell treatment, reducing toxicities, and maintaining the function of CAR-T cells.

SUBMITTER: Zhang H

PROVIDER: S-EPMC8973323 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-6/IFN-γ double knockdown CAR-T cells reduce the release of multiple cytokines from PBMCs in vitro.

Zhang Huihui H Lv Xiaofei X Kong Qunfang Q Tan Yi Y

Human vaccines & immunotherapeutics 20220120 1

CD19-targeted chimeric antigen receptor T (anti-CD19 CAR-T) cells have shown good therapeutic results in the treatment of CD19 + B cell acute lymphocytic leukemia and lymphoma. However, severe side reactions and cytotoxicity are great challenges in the application of anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) is the main side effect of CAR-T cell treatment, and interleukin-6 (IL-6) and interferon γ (IFN-γ) are cytokines that play major roles in CRS. Therefore, we investigated ...[more]

PMID: 35049413

Similar Datasets

Project description:The clinical features of psoriasis, characterized by sharply demarcated scaly erythematous plaques, are typically so distinctive that a diagnosis can easily be made on these grounds alone. However, there is great variability in treatment response between individual patients, and this may reflect heterogeneity of inflammatory networks driving the disease. In this study, whole-genome transcriptional profiling was used to characterize inflammatory and cytokine networks in 62 lesional skin samples obtained from patients with stable chronic plaque psoriasis. We were able to stratify lesions according to their inflammatory gene expression signatures, identifying those associated with strong (37% of patients), moderate (39%) and weak inflammatory infiltrates (24%). Additionally, we identified differences in cytokine signatures with heightened cytokine-response patterns in one sub-group of lesions (IL-13-strong; 50%) and attenuation of these patterns in a second sub-group (IL-13-weak; 50%). These sub-groups correlated with the composition of the inflammatory infiltrate, but were only weakly associated with increased risk allele frequency at some psoriasis susceptibility loci (e.g., REL, TRAF3IP2 and NOS2). Our findings highlight variable points in the inflammatory and cytokine networks known to drive chronic plaque psoriasis. Such heterogeneous aspects may shape clinical course and treatment responses, and can provide avenues for development of personalized treatments. We used Affymetrix microarrays to evaluate genome-wide expression in primary human keratinocytes exposed to cytokines. Cytokine activity signatures were used to interpret the shifts in gene expression that occur in psoriasis plaques relative to normal uninvolved skin. Primary keratinocytes from three donors (subjects 1, 2, and 3) were obtained and were either untreated (control) or exposed to cytokines (IL-4, IL-13, IFN-alpha, IFN-gamma and TNF). For the IL17A samples, primary keratinocytes were obtained from six donors, with cells derived from three donors treated with IL-17A and cells derived from the other three donors left untreated (i.e., unpaired control samples).

Dataset Information

IL-6/IFN-γ double knockdown CAR-T cells reduce the release of multiple cytokines from PBMCs in vitro.

Publications

IL-6/IFN-γ double knockdown CAR-T cells reduce the release of multiple cytokines from PBMCs in vitro.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets