Humoral and cellular responses of colorectal cancer patients treated with monoclonal antibodies and interferon gamma.
Fifteen patients with metastatic gastrointestinal adenocarcinomas were treated with low doses of recombinant human interferon gamma (rh-IFN gamma) and a mixture of monoclonal antibodies (mAb) that bind to tumor cells. All antibodies were of the IgG2a isotype and interact with human effector cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Natural killer lysis against K562 cells by peripheral blood mononuclear cells purified from patients' blood was enhanced in all patients at day 3 during IFN gamma treatment. Monocytes from two patients had increased ADCC levels. Increase in the percentage of monocytes able to bind mouse IgG2a was detected by Fc receptor flow cytometry analysis 24 h after the first IFN gamma infusion. However, 3 days later, the percentage of fluorescent cells had fallen below baseline levels. The analysis of patients' sera showed that at day 2 after mAb infusion, only 50% of the circulating mouse IgG was immunoreactive, and after 1 week, only traces of immunoreactive mouse IgG were detected. All patients developed a human anti-(mouse Ig) response of IgG, IgM and IgA isotypes, although only low levels of anti-idiotypic antibodies were detected at the time of testing (up to 9 weeks) after mAb infusion. No difference in the IgG subclasses of anti-(mouse Ig) antibody was observed between patients treated with mAb and IFN gamma and patients treated with mAb alone.
Blottiere
H M
HM
INSERM U211 Faculte de Medecine, Nantes, France.
Douillard
J Y
JY
Koprowski
H
H
Steplewski
Z
Z
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D007371:Interferon-gamma