Cytokines as adjuvants: effect on the immunogenicity of NeuAc alpha 2-6GalNAc alpha-O-Ser/Thr (sialyl-Tn).
Sialyl-Tn, defined by monoclonal antibody (MAb) B72.3, shows restricted normal-tissue distribution but is expressed in a wide variety of carcinomas. To analyze the immunogenicity of sialyl-Tn, mice were immunized with ovine submaxillary mucin (OSM) in combination with monophosphoryl lipid A (MPLA), liposomes, or adjuvants that activate macrophages (rIL-1, rIFN-gamma, rM-CSF, IL-1-derived peptides) or T cells (rIL-2). The level and specificity of the immune response were analyzed by ELISA. rIL-1 and rIFN-gamma induced a very high and specific antibody response, whereas the effect of rM-CSF was dose-dependent: at a low dose it induced a high-level specific antibody response and at the high dose level it induced a polyclonal non-specific response. These results indicate that cytokines are powerful adjuvants which modulate both the magnitude and specificity of the immune response. More studies are necessary to determine the optimal doses in animal models and in active specific immunotherapy of patients with cancer.
Piera
M
M
Department d'Immunologia, Universitat Autònoma de Barcelona, Spain.
de Bolós
C
C
Castro
R
R
Real
F X
FX
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D015295:Antigens, Tumor-Associated, Carbohydrate; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D008050:Lipid A; D009077:Mucins; D011994:Recombinant Proteins; C055491:sialosyl-Tn antigen; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; C048436:monophosphoryl lipid A