Induction of CA125-specific B and T cell responses in patients injected with MAb-B43.13--evidence for antibody-mediated antigen-processing and presentation of CA125 in vivo.
The murine monoclonal anti-CA125 antibody MAb-B43.13 has previously been administered as an immunoscintigraphic agent in order to monitor recurrence of ovarian cancer in patients, and a long-term follow-up demonstrated a survival benefit for these patients. The clinical benefit was initially attributed to the activation of the idiotypic network. The objective of this study was to investigate the role of CA125-MAb-B43.13 immune complex formation on the induction of CA125-specific immune responses. Analysis of patient serum samples from pharmacokinetic studies demonstrated that the antibody forms immune complexes with CA125 in circulation within 30 minutes of injection. Induction of humoral and cellular anti-CA125 responses correlated with the amount of circulating CA125 antigen present at time of antibody injection. Subsequent to the injection of MAb-B43.13, the patients generated anti-CA125 antibodies that were directed against various epitopes on the antigen and were not restricted to the specific epitope recognized by MAb-B43.13. The generation of CA125-specific B and T cell responses after MAb-B43.13 injection correlated with improved survival. The influence of circulating CA125 for the induction of CA125-specific immune responses and the multi-epitopic nature of the human anti-CA125 antibodies suggest that the majority of these antibodies were not induced via the idiotypic network but by the autologous antigen itself. Since antibody and T cell responses to CA125 were not present before injection of MAb-B43.13, it is hypothesized that complex formation of MAb-B43.13 with circulating antigen triggers the induction of CA125-specific immune responses.
Noujaim
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AA
AltaRex Corp., 1123 Dentistry-Pharmacy, University of Alberta, Edmonton, AB, T6G 2N8, Canada. tnoujaim@altarex.com
Schultes
B C
BC
Baum
R P
RP
Madiyalakan
R
R
D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D018394:CA-125 Antigen / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007275:Injections, Intravenous; D008213:Lymphocyte Activation; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018394:CA-125 Antigen; D000949:Histocompatibility Antigens Class II; C107428:oregovomab