A biomimetic SPARC platform coupling adaptor recruitment and BRS-Lck condensation for enhanced NK/T cell combination therapy

SPARC receptors in NK cells enhance antigen-specific tumor killing by using NCR1–Lck condensates formed via two BRS motifs to promote receptor clustering and cytotoxicity.

• Why it matters: Classical CAR-like designs can raise tonic signaling and limit persistence, while endogenous receptor recognition constraints restrict targeting flexibility.
• What they did: The authors engineered Synthetic Parallel Antigen Receptor Complexes (SPARC) using NCR1 and a TCR chain to recruit endogenous CD3{zeta}/FcR{gamma}, then tested how NCR1 cytoplasmic BRS motifs drive Lck condensation and signaling.
• The result: SPARC-engineered T cells and NK cells together show superior efficacy versus either cell type alone, and adding costimulatory domains further improves SPARC performance.

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