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

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 gamma (IFN-gamma) are cytokines that play major roles in CRS. Therefore, we investigated double knockdown (KD) of IL-6 and IFN-gamma 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-gamma 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.

Automated summary

In the treatment of CD19 + B cell acute lymphocytic leukemia and lymphoma, a potential strategy of double knockdown of IL-6 and IFN-gamma has been investigated to manage the severe side effects of anti-CD19 CAR-T cell therapy, such as cytokine release syndrome. This improved therapy reduces cytokine release, thereby improving the safety and efficacy of CAR-T cell treatment.