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TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed. We have previously shown that TNF autovaccination successfully generates high anti-TNF antibody titres, blocks TNF and ameliorates collagen-induced arthritis in DBA/1 mice. In this study, we examined the ability of TNF autovaccination to generate anti-TNF antibody titres and block metastasis in the murine B16F10 melanoma model. We found that immunisation of C57BL/6 mice with TNF autovaccine produces a 100-fold antibody response to TNF compared to immunisation with phosphate-buffered saline vehicle control and significantly reduces both the number (P<0.01) and size of metastases (P<0.01) of B16F10 melanoma cells. This effect is also observed when an anti-TNF neutralising monoclonal antibody is administered, confirming the essential role TNF plays in metastasis in this model. This study suggests that TNF autovaccination is a cheaper and highly efficient alternative that can block TNF and reduce metastasis in vivo and trials with TNF autovaccination are already underway in patients with metastatic cancer.

Original publication

DOI

10.1038/sj.bjc.6601670

Type

Journal article

Journal

British Journal of Cancer

Publication Date

03/2004

Volume

90

Pages

1279 - 1284

Addresses

Department of Cancer Medicine, Faculty of Medicine, Chelsea and Westminster Hospital, 369 Fulham Rd, Imperial college School of Medicine, London SW10 9NH, UK. a.waterston@blueyonder.co.uk

Keywords

Animals, Mice, Inbred C57BL, Mice, Melanoma, Skin Neoplasms, Neoplasm Metastasis, Disease Models, Animal, Tumor Necrosis Factor-alpha, Antineoplastic Agents, Vaccination, Antibody Formation, Male