Interleukin-6 fused to an anti-idiotype antibody in a vaccine increases the specific humoral immune response against CA125+ (MUC-16) ovarian cancer.
Anti-idiotypic (Id) monoclonal antibodies can serve as surrogate for tumor-associated antigens in vaccination strategies. The murine anti-Id monoclonal antibody ACA125 that mimics the CA125 carbohydrate antigen expressed on ovarian cancer cells induces an anti-anti-Id antibody (Ab3) response that is associated with prolonged survival of ovarian cancer patients. To increase the Ab3 antibody response, we evaluated two strategies in a mouse model: (a) coinjection of human interleukin (IL)-6 together with the fusion protein chACA125, which consists of the anti-Id ACA125 single-chain Fv antibody joined to the human IgG1 CH2/CH3 domain; and (b) injection of the fusion protein chACA125-IL-6, which consists of the ACA125 single-chain Fv fused to human IL-6 via the IgG1 CH2/CH3 domain. Vaccination of mice with the chACA125-IL-6 fusion protein resulted in higher titers of anti-CA125 (Ab3) antibodies compared with application of the chACA125 antibody with or without systemic coadministration of IL-6. Application of the chACA125-IL-6 fusion protein did not elicit detectable antihuman IL-6 antibody titers, whereas coinjection of human IL-6 did. Taken together, these data suggest that the chACA125-IL-6 fusion protein directly stimulates ACA125-specific B cells via the IL-6 domain, whereas coinjection of IL-6 leads to an overall immune stimulation. Antigen-IL-6 fusion proteins will improve vaccination regimens and anticancer immunotherapeutic strategies by increasing the antigen-specific humoral immune response.
Reinartz
Silke
S
Center of Obstetrics and Gynecology, University of Marburg, 35037 Marburg, Germany. silke.reinartz@med.uni-marburg.de
Hombach
Andreas
A
Köhler
Siegmund
S
Schlebusch
Harald
H
Wallwiener
Diethelm
D
Abken
Hinrich
H
Wagner
Uwe
U
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018394:CA-125 Antigen / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D018796:Immunoconjugates / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D016233:Immunotherapy, Active; D015850:Interleukin-6 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D013045:Species Specificity
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018394:CA-125 Antigen; D019496:Cancer Vaccines; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D015850:Interleukin-6; D011993:Recombinant Fusion Proteins