SPPL3-Knockout CAR-T Cells

Universal Allogeneic Type

By deleting SPPL3, T-cell glycosylation is altered to achieve immune evasion of allogeneic CAR-T cells while retaining TCR for in vivo persistence.

Wu, Zeguang · Liu, Yang · Tang, Wei · Yang, Qingming · Wenjuan, Zheng · Wu, Zhiqiang · Wang, Yao · Wong, Catherine C.L. · Yuan, Pengfei · Han, Weidong · Wei, Wensheng

Cell 2025

Specifications

Grade ≥3 CRS rate

{'zh': '3/9', 'en': '3/9'}

Advantages

Immune evasion without functional loss

SPPL3 deletion alters glycosylation, restricts ligand accessibility, and reduces allogeneic immunity without compromising anti-CD19 CAR function.

TCR retention supports persistence

Reverse translational research highlighted the pivotal role of TCR in sustaining T cell persistence, so SPPL3-null TCR-sufficient CAR-T cells may persist longer in vivo.

No graft-versus-host disease

No clinical signs of graft-versus-host disease were observed in three patients with lymphoma or leukemia treated with SPPL3-null, TCR-sufficient CAR-T cells.

Applications

• Off-the-shelf cell therapy：Thaw-and-use without HLA matching, reducing treatment delay
• Allogeneic CAR-T：Glycan-mediated immune evasion enables universal donor cells
• Immune evasion engineering：SPPL3 deletion modifies glycans to limit ligand accessibility
• Cell therapy safety：TCR sufficient yet no graft-versus-host disease observed