Human anti-murine immunoglobulin responses and immune functions in cancer patients receiving murine monoclonal antibody therapy.
In our institution, over 200 patients with gastro-intestinal tract carcinomas have been treated with monoclonal antibodies (MAbs) including CO 17-1A. In one clinical trial, MAbs were administered in combination with gamma interferon. Natural killer cell cytotoxicity (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) were studied in patients before treatment. Very low NK and ADCC activities were measured in metastatic cancer patients. NK cell lysis was enhanced during gamma-interferon treatment, associated with a modification of the Fc receptor expression, but no changes in the ADCC reactivities of leukocytes were noticed. Monoclonal antibodies were circulating for one to four weeks after a single dose infusion, independent of the patients' immune responses toward the administered MAb. Sixty-three percent of the patients mounted an anti-mouse immunoglobulin response. Anti-idiotypic antibodies were detected in 70% of the responding patients. Variations in the anti-mouse Ig responses were dependent on the therapeutic protocol. The immune responses were composed of IgM, IgA, and IgG (mainly IgG1, often associated with IgG2 and/or IgG3). In patients receiving MAbs together with gamma-interferon, development of the anti-mouse Ig responses were delayed with an increase in the anti-isotypic component and a decrease in the anti-idiotypic component as compared to patients treated with MAb alone. No correlation could be established with clinical results.
Blottière
H M
HM
INSERM U211, Faculté de Médecine, Nantes, France.
Steplewski
Z
Z
Herlyn
D
D
Douillard
J Y
JY
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D003602:Cytotoxicity, Immunologic; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011961:Receptors, Fc / Q000032:analysis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D011961:Receptors, Fc; D007371:Interferon-gamma