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Thomas Sydenham "The British Hippocrates".

1995/03/01 by J M Pearce · 2 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Biochemistry #Biology #Cancer research #Cell death mechanisms and regulation #Chemokine #Cytokine #Gene #Gene expression #Immunology #Inflammation #PARP inhibition in cancer therapy #Phagocytosis and Immune Regulation #Psychological repression #Secretion #Tumor cells #Tumor microenvironment

paper · pdf · doi:10.1136/jnnp.58.3.292

openalex publication_date 1995/03/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/04/21

Abstract

<h3>Abstract</h3> Capacity of tumor niche chemotaxis and long-term persistency making macrophage as great vehicles for anti-tumor factor delivery. Macrophages-based delivery of chemokines or cytokines have been tested for tissue homeostasis and cancer repression. TRAIL as a promising anti-tumor cytokine, made little clinical progress due to limited stability and off-target toxicity. Here we engineered macrophages with tumor micro-environment (TME)-induced trimerized CP1-TRAIL secretion under the TME specific promoter Arg1 (Tri-TRAIL-iM). The Tri-TRAIL-iM cells displayed high specific inducible activity in both cell-based co-culture assay and in tumor baring mice models. Compared to normal TRAIL over-expressed macrophages under none-inducible promoter, Tri-TRAIL-iM infiltrated to tumor sites and showed superior apoptosis induction of cancer cells and tumor growth repression as well as less systemic side effect. This inducible delivery TRAIL strategy can be effectively further applied in clinical studies and can be coupled with other engineered methods to maximize the therapeutic outcomes for solid tumors.

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