Generation of tumour-rejecting anti-carbohydrate monoclonal antibodies using melanoma modified with Fas ligand.
Carbohydrate antigens such as glycolipids and glycoproteins are over-expressed in a variety of cancers and have therefore been identified as ideal candidates for tumour vaccines. Detection of anti-carbohydrate antibodies is associated with a good prognosis in cancer patients. However, generation of an efficient adaptive immune response has been hampered by the low immunogenicity of carbohydrates due to tolerance. Here, we describe a method by which tumour-rejecting antibodies directed against carbohydrates can be elicited in two different melanoma mouse models. Thus, using the murine melanoma B16F10 over-expressing Fas ligand (FasL), we have generated mAbs against cancer carbohydrate antigens expressed by the melanoma. Importantly, passive transfer of mAbs resulted in rejection of melanoma in vivo. Their protective effect in vivo was dependent on FcR and in vitro antibody-dependent cellular phagocytosis. They were also able to delay tumour growth when injected after the tumour was established. FasL-expressing tumours as an adjuvant are a novel way to generate anti-carbohydrate antibodies able to reject tumours in vivo.
Simon
A Katharina
AK
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, UK. katja.simon@ndm.ox.ac.uk
Newsom-Davis
Tom
T
Frayne
Matthew E F
ME
Ch'en
Paul F-T
PF
McMichael
Andrew J
AJ
Screaton
Gavin R
GR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000096:biosynthesis*; D000918:Antibody Specificity / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D045744:Cell Line, Tumor; D053222:Fas Ligand Protein / Q000276:immunology*; D006801:Humans; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000172:deficiency / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D053222:Fas Ligand Protein; C485701:Fcgr1 protein, mouse; D017452:Receptors, IgG