Extended Data Fig. 9: Vector design and CAR construct of ESO-T01. | Nature Medicine

Extended Data Fig. 9: Vector design and CAR construct of ESO-T01.

From: In vivo generation of anti-BCMA CAR-T cells in relapsed or refractory multiple myeloma: a phase 1 study

Extended Data Fig. 9: Vector design and CAR construct of ESO-T01.

a, Vector design features of ESO-T01. An anti-TCR nanobody (VHH) targets the TCR/CD3 complex to confer T-cell specificity. A mutant VSVG (ENV) envelope reduces broad tropism and lowers immunogenicity. High CD47 expression decreases clearance by the mononuclear phagocyte system, enhancing persistence and transduction. Knockout of MHC class I reduces immunogenicity and susceptibility to complement- or antibody-mediated inactivation. A synthetic T cell–specific promoter (SYN) restricts expression to T cells, while the BCMA CAR backbone is derived from the clinically validated PRG1801 second-generation VHH CAR. b, CAR construct of ESO-T01. The CAR contains an anti-BCMA VHH for antigen recognition, a CD8 hinge and transmembrane domain (TMD) for structural stability, the 4-1BB costimulatory domain, and the CD3ζ signaling domain for T-cell activation. Abbreviations: CAR, chimeric antigen receptor; BCMA, B Cell Maturation Antigen; MHC, Major Histocompatibility Complex; SYN, Synthetic T cell-specific Promoter; TCR, T Cell Receptor; VHH, Variable Domain of Heavy-chain Antibodies; VSVG, Vesicular Stomatitis Virus Glycoprotein.

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