FDA official logo
GSRS logoPFDA official logo

VOLAMCABTAGENE DURZIGEDLEUCEL

UNII:S5TX5E9EWP
Type:INGREDIENT SUBSTANCE
Formula:
Preferred Substance Name:VOLAMCABTAGENE DURZIGEDLEUCEL
GSRS Full Record:
S5TX5E9EWP
i

  • ALLOGENEIC T CELLS OBTAINED FROM PERIPHERAL BLOOD BY LEUKAPHERESIS, GENETICALLY MODIFIED BY CRISPR/CAS9 (CLUSTERED REGULARLY INTERSPACED SHORT PALINDROMIC REPEATS/CRISPR-ASSOCIATED PROTEIN 9) MEDIATED GENE EDITING CONSISTING OF THREE GUIDE RNAS (GRNAS) INTRODUCED TRANSIENTLY AS CAS9-GRNA RIBONUCLEOPROTEIN (RNP) COMPLEX FOR THE TARGETED DISRUPTION OF THE T CELL RECEPTOR ALPHA CHAIN CONSTANT (TRAC), .BETA.2 MICROGLOBULIN (B2M) AND THE CLUSTER OF DIFFERENTIATION 70 (CD70) LOCI AND INSERTION OF AN ANTI-CD70 CHIMERIC ANTIGEN RECEPTOR (CAR) TRANSGENE INTO THE TRAC LOCUS VIA AN ADENO-ASSOCIATED VIRUS SEROTYPE 6 (AAV6) VECTOR. THE CAR IS COMPOSED OF A SIGNAL PEPTIDE SEQUENCE FROM HUMAN CD8A, AN ANTI-CD70 SINGLE-CHAIN VARIABLE FRAGMENT (SCFV) DERIVED FROM ANTI-CD70 HYBRIDOMA 1F6, A CD8 HINGE AND TRANSMEMBRANE DOMAIN, AND THE 4-1BB AND CD3.ZETA. CO-STIMULATORY DOMAINS. EXPRESSION OF THE CAR IS DRIVENBY THE ELONGATION FACTOR 1 ALPHA (EF-1.ALPHA.) PROMOTER AND IS TERMINATED BY A SYNTHETIC POLYADENYLATION (POLYA) SEQUENCE. THE ANTI-CD70 CAR EXPRESSION CASSETTE IS FLANKED BY TWO TRAC HOMOLOGY ARMS GUIDING THE EXPRESSION CASSETTE TO THE TRAC LOCUS AND THE LEUKOPHERESIS MATERIAL IS ENRICHED FOR T CELLS USING CD4/CD8 SELECTION AND ACTIVATED WITH ANTI-CD3/CD28 ANTIBODY-COATED BEADS. T CELLS ARE CULTURED IN THE PRESENCE OF GROWTH MEDIA CONTAINING HUMAN SERUM, INTERLEUKIN 2 (IL-2) AND 7 (IL-7). THE FINAL T CELLS ARE 30% CAR+ T CELLS, 0.4% TCR+, 2% CD70+, AND 30% B2M+ AND SECRETE INTERFERON GAMMA (IFN.GAMMA.) AND IL-2 WHEN CO-CULTURED WITH CD70 EXPRESSING CELL
  • CTX-130
  • CTX130
  • volamcabtagene durzigedleucel [INN]




UNII - S5TX5E9EWP | UNII Search Service