NEUTRALIZATION OF HUMAN CYTOKINES WITH MEMBRANE-BOUND ANTI-CYTOKINE NON-SIGNALING BINDERS EXPRESSED IN IMMUNE CELLS

摘要

Transgenic T cells and vectors for making transgenic T cells are described. The vectors can include a nucleic acid encoding a membrane-bound anti-IL6 (mb-alL6) single chain variable fragment (scFv), and the transgenic T cells can express mb-alL6. The transgenic T cells are useful for suppressing proliferation of IL-6-dependent cells, reducing IL-6 concentration, or both. In one embodiment, the vector is a bicistronic construct encoding the mb-alL6 and an anti- CD19-41 ΒΒ-003ζ chimeric antigen receptor (CAR). In another embodiment, an anti-IL-6 scFv can be linked to a 41 BB and 003ζ domains to form an anti-IL-6 CAR. The transgenic T cells expressing said constructs can reduce the risk of cytokine release syndrome (CRS) in cancer patients being treated with CAR T cell or for the treatment of autoimmune diseases and inflammatory diseases in which cytokines are involved in pathogenesis.