Tumor cells expressing membrane-bound tumor necrosis factor activate macrophages and have a compromised growth in immunosuppressed and immunodeficient mice.
Tumor necrosis factor (TNF)-alpha 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.
Nagy
Tünde
T
Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
Glavinas
Hristos
H
Szincsák
Nóra
N
Hunyadi
János
J
Jánossy
Tamás
T
Duda
Ernö
E
Vizler
Csaba
C
Juhász
István
I
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D018920:Coculture Techniques; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007108:Immune Tolerance; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010587:Phagocytosis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha