Axicabtagene ciloleucel

The CD 19 antigen is an integral membrane glycoprotein normally expressed in B cells during differentiation; however, it is often aberrantly expressed on B cells that have undergone a neoplastic transformation. Distinctive expression of CD19 in lymphomas and leukemias makes this glycoprotein a good immunotherapeutic target.

Axicabtagene ciloleucel is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy. It consists of genetically modified T cells of the patient receiving the immunotherapy. The manufacturing of axicabtagene ciloleucel begins with the collection of peripheral blood mononuclear cells from the patient, followed by the harvesting and genetic modification of T cells ex vivo. Retroviral transduction is used to express a CAR on T cells, creating anti-CD19 CAR T cells that are then expanded. Axicabtagene ciloleucel, a suspension of anti-CD19 CAR T cells, is infused back into the patient during treatment. Axicabtagene ciloleucel is made up of two components: a single-chain variable fragment targets the CD19 proteins, and there are intracellular domains - CD28 and CD3-zeta co-stimulatory domains - that signal T-cell activation. Once administered into the patient's bloodstream, axicabtagene ciloleucel recognizes the CD19-expressing target cells and the intracellular domains of the drug activate the downstream signalling cascades that lead to T-cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines that kill cancer cells. Axicabtagene ciloleucel binds to CD19-expressing cancer cells and normal B cells.