Reference - Detail
| RRC ID | 83380 |
|---|---|
| Author | Nii T, Yoshimi T, Tanito K, Hijii S, Takata H, Kishimura A, Mori T, Ishida T, Katayama Y. |
| Title | Inflammation-triggering Engineered Macrophages (MacTriggers) Are Promising Cell-based Therapeutic Avenues for Chemoresistant Solid Tumors. |
| Journal | Anticancer Res |
| Abstract |
BACKGROUND/AIM:Chimeric antigen receptor T-cell therapy has shown efficacy against chemoresistant B-cell leukemia and lymphoma but is limited in solid tumors. This study proposes using inflammation-triggering engineered macrophages (MacTriggers) to target chemoresistant tumors. Intravenous MacTriggers infiltrate tumors, inducing inflammation via tumor necrosis factor-alpha (TNF-α), converting the immunosuppressive microenvironment into an immuno-active state, and enhancing anti-tumor immune responses. MATERIALS AND METHODS:DOX-resistant murine colon cancer cells (DOX-Resi) were established by repeated in vivo exposure to DOX. IC50 values and mRNA expression of Abcb1a (encoding P-gp) in WT or DOX-Resi cells were evaluated by qPCR. MacTriggers were engineered to release TNF-α upon sensing tumor-associated arginase 1 (Arg1) activity. BALB/c mice with subcutaneous DOX-Resi tumors received intravenous MacTriggers or DOX. Tumor growth, histological changes, and side effects, including cardiotoxicity, were assessed via tumor volume monitoring, immunohistochemistry, and serum cardiac troponin-I measurement. RESULTS:DOX-Resi cells had an IC50 value approximately 2.5 times higher than WT cells, with significantly higher Abcb1a expression. MacTriggers significantly suppressed DOX-Resi tumor growth, while DOX showed limited efficacy. MacTrigger administration did not cause severe side effects, unlike DOX, which induced cardiotoxicity. CONCLUSION:MacTriggers offer a novel, effective, and safer therapeutic approach for chemoresistant solid tumors, addressing chemotherapy limitations and improving outcomes in drug-resistant cancers. |
| Volume | 45(4) |
| Pages | 1395-1405 |
| Published | 2025-4-1 |
| DOI | 10.21873/anticanres.17525 |
| PII | 45/4/1395 |
| PMID | 40155021 |
| MeSH | Animals Cell Line, Tumor Cell- and Tissue-Based Therapy / methods Colonic Neoplasms / drug therapy Colonic Neoplasms / genetics Colonic Neoplasms / immunology Colonic Neoplasms / pathology Colonic Neoplasms / therapy Doxorubicin* / pharmacology Drug Resistance, Neoplasm* Female Humans Inflammation* / pathology Macrophages* / drug effects Macrophages* / immunology Macrophages* / metabolism Mice Mice, Inbred BALB C* Tumor Microenvironment / drug effects Tumor Necrosis Factor-alpha / metabolism |
| IF | 1.994 |
| Resource | |
| Human and Animal Cells | Colon-26(RCB2657) |