ZAMTOCABTAGENE AUTOLEUCEL

AUTOLOGOUS T CELLS OBTAINED FROM PERIPHERAL BLOOD COLLECTED BY LEUKAPHERESIS, TRANSDUCED WITH A NON-REPLICATING LENTIVIRAL VECTOR, PSEUDOTYPED WITH VESICULAR STOMATITIS VIRUS (VSV) GLYCOPROTEIN (G), ENCODING A CODON-OPTIMIZED CHIMERIC ANTIGEN RECEPTOR (CAR) TARGETING THE HUMAN B-LYMPHOCYTE ANTIGENS CD19 AND CD20 CELLS ARE ACTIVATED IN THE PRESENCE OF A COLLOIDAL POLYMERIC NANOMATRIX COVALENTLY ATTACHED TO ANTI-CD3 AND ANTI-CD28, TRANSDUCED, AND THEN CULTURED IN THE PRESENCE OF IL-7 AND IL-15. THE T CELLS ARE PREDOMINANTLY CENTRAL MEMORY (>80%; CD4+/CD8+, CD62L+, CD45RO+) AND EFFECTOR MEMORY T CELLS (CD4+/CD8+, CD62L-, CD45RO+). THE TARGET BINDING MOIETIES OF THE CAR ARE TWO SINGLE-CHAIN VARIABLE FRAGMENTS (SCFV), DERIVED FROM A MURINE ANTI-HUMAN CD20 AND A MURINE ANTI-HUMAN CD19 HYBRIDOMA CLONE LINKED WITH A (GGGGS)5 SEQUENCE, FUSED TO INTRACELLULAR SIGNALING DOMAINS FROM 4-1BB AND CD3 ZETA, UNDER THE CONTROL OF THE ELONGATION FACTOR 1 ALPHA (EF1.ALPHA.) PROMOTER. THE GENOME ALSO CONTAINS A 5' SPLICE DONOR SITE AND A 3' SPLICE ACCEPTOR SITE, A GAG TRUNCATED OPEN READING FRAME, AN ENV TRUNCATED OPEN READING FRAME, A REV RESPONSE ELEMENT (RRE) 5' TO THE TRANSGENE, AND A NON-CODING ARTIFICIAL SEQUENCE FOR VIRAL TITRE DETERMINATION AND A NEF TRUNCATED OPEN READING FRAME 3' TO THE TRANSGENE zamtocabtagene autoleucel [INN] Zamtocabtagene autoleucel [WHO-DD]