TRAC and Power3 (SPPL3) Genes Knock-out Allogeneic CD19-targeting CAR-T Cell Therapy in r/r B-NHL

Summary

ATHENA chimeric antigen receptor (CAR)-T, a CD19-directed CAR-T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL). The cells are from healthy adult volunteer donors that are knocked out of TRAC and Power3 (SPPL3) genes ex vivo using CRISPR-Cas9 gene editing components. In this study, a second-generation anti-CD19 CAR prototype was constructed, bearing murine FMC63 single-chain variant fragment (scFv) together with intracellular CD28 co-stimulatory and CD3ζ signaling domains linked by a CD28 sequence comprising the hinge and transmembrane domains. This is a single center, prospective, open-label, single-arm, phase 1/2 study. A total of around 30 patients with r/r B-cell NHL will be enrolled in the study and receive allogeneic CD19-CAR-T cell infusion. Phase 1 (n=6 to 18) is a dose escalation part, and phase 2 (n=10 to 12) is a expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of ATHENA CAR-T cell therapy in patients with r/r B-cell NHL.

Timeline

Start

2023-09-06

Primary completion

2025-09-01

Completion

2026-09-01

Outcome

Met primary endpoint

paper SPPL3-null, T cell receptor (TCR)-deficient anti-CD19 allogeneic CAR-T cells reached the safety primary endpoint PMID 40845838 ↗

Publications

• Wu Z, Shi J, Lamao Q, Qiu Y, Yang J, Liu Y, Liang F, Sun X, Tang W, Chen C, Yang Q, Wang C, Li Z, Zhang H, Yang Z, Zhang Y, Yi Y, Zheng X, Sun Y, Ma K, Yu L, Yang H, Wang Z, Zheng W, Yang L, Zhang Z, Zhang Y, Wu Z, Wang Y, Wong CCL, Jin M, Yuan P, Han W, Wei W. Glycan shielding enables TCR-sufficient allogeneic CAR-T therapy. Cell. 2025 Oct 30;188(22):6317-6334.e21. doi: 10.1016/j.cell.2025.07.046. Epub 2025 Aug 21.

Drugs

Indications