title: Granulocyte/macrophage-colony-stimulating factor augments the induction of antibodies, especially anti-idiotypic antibodies, to therapeutic monoclonal antibodies.
abstract: A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17-1A-treated patients (n = 76) developed antibodies against both idiotypic and isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti-idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated patients, 16 developed type I allergic reactions. These patients had significantly higher concentrations of anti-(mouse Ig) antibodies than patients without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone; they constituted 9% of this group (5/56). The remaining 11 patients had been given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group (11/20). The difference was statistically significant (P < 0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2 concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab2 concentration (at least 15 micrograms/ml) 1 month after completion of mAb therapy responded to mAb treatment as compared to those with a low ab2 concentration (P < 0.05). Moreover, patients with a high ab2 concentration (at least 15 micrograms/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P = 0.01).
authors.affiliation: Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Ragnhammar
authors.forename: J
authors.initials: J
authors.lastname: Fagerberg
authors.forename: J E
authors.initials: JE
authors.lastname: Frödin
authors.forename: P
authors.initials: P
authors.lastname: Wersäll
authors.forename: L O
authors.initials: LO
authors.lastname: Hansson
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000096:biosynthesis* / Q000097:blood; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000097:blood; D007167:Immunotherapy; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007132:Immunoglobulin Isotypes; D000922:Immunotoxins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor