Definition

A preparation of T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 and containing a short hairpin RNA (shRNA) against the pro-inflammatory cytokine interleukin-6 (IL-6), and linked to the intracellular signaling domains of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (TCRzeta; CD247; CD3zeta), with potential immunostimulating and antineoplastic activities. Upon administration, short hairpin RNA-IL-6 gene silencing anti-CD19 CAR T cells target and bind to CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. IL-6 gene silencing reduces IL-6 gene expression and release. This may inhibit IL-6-mediated toxicity due to high IL-6 levels and may prevent severe cytokine release syndrome (CRS) and CAR-T-related encephalopathy (CRES).