title: TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model.
abstract: 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.
authors.affiliation: 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
authors.forename: A M
authors.initials: AM
authors.lastname: Waterston
authors.forename: F
authors.initials: F
authors.lastname: Salway
authors.forename: E
authors.initials: E
authors.lastname: Andreakos
authors.forename: D M
authors.initials: DM
authors.lastname: Butler
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000276:immunology* / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000627:therapeutic use*; D014611:Vaccination
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha