Tumor cells expressing membrane-bound tumor necrosis factor activate macrophages and have a compromised growth in immunosuppressed and immunodeficient mice

• Published in: Cancer letters 2003-06, Vol.196 (1), p.49-56
• Main Authors: Nagy, Tünde, Glavinas, Hristos, Szincsák, Nóra, Hunyadi, János, Jánossy, Tamás, Duda, Ernö, Vizler, Csaba, Juhász, István
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Biological activity; Biological and medical sciences; Cell culture; Cell Membrane - chemistry; Coculture Techniques; Cytotoxicity; Experiments; Female; HeLa Cells; Herpes viruses; Humans; Immune Tolerance; Macrophage tumor killing; Macrophages - metabolism; Medical sciences; Melanoma; Membrane-bound tumor necrosis factor; Mice; Mice, Inbred CBA; Mice, SCID; Neoplasm Transplantation; Phagocytosis; Severe combined immunodeficient mice; Tumor gene therapy; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - immunology
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(03)00181-2

Tumor necrosis factor (TNF)-α producing tumors as vaccines were demonstrated to induce a therapeutic anti-tumor immune response, but their clinical use is limited by the toxicity of soluble TNF. We investigated the growth characteristics and immunomodulatory properties of HeLa cells producing an uncleavable transmembrane form of TNF (preTNF). The growth of the transformed tumors was compromised in both immunosuppressed and severe combined immunodeficient mice; no signs of TNF toxicity were detected. Macrophages co-cultured with the transformed cells showed increased phagocytosis and cytokine production, indicating that activated macrophages may be the mediators of the anti-tumor effect. preTNF producing tumor cells are promising safe anti-tumor vaccine candidates.