Engineered cryo-shocked tumor cells recruit T cells for lung cancer immunotherapy.

Abstract

Immune checkpoint blockade has transformed cancer therapy, yet its efficacy against solid tumors remains constrained by poor T cell infiltration and an immunosuppressive tumor microenvironment. Achieving localized and sustained chemokine signaling without systemic immune toxicity remains a central unmet challenge for cytokine-based immunotherapy. Here, we presented a cryo-engineered bio-depot platform derived from liquid‑nitrogen-treated (LNT) tumor cells for the site-restricted and controlled delivery of protein therapeutics. The cryo-shocked process preserves cellular integrity and protein bioactivity while abolishing pathogenicity of tumor cells, generating a versatile vehicle for therapeutic payloads. Applying this platform, we constructed LNT depots expressing C-X-C motif ligand 9 (CXCL9), which established a persistent chemokine gradient within the lung after intravenous injection, leading to robust T cell recruitment and augmented tumor growth inhibition. Furthermore, we demonstrated the platform adaptability by engineering LNT cells to secrete aPD-1, which significantly prolonged survival in a murine orthotopic lung cancer model. This cryo-engineered depot integrates the structural fidelity of biomaterials with the functional complexity of living systems, offering a generalizable route for personalized protein therapeutics in cancer immunotherapy.