title: Human antibody response to the intravenous and intraperitoneal administration of the F(ab')2 fragment of the OC125 murine monoclonal antibody.
abstract: We have characterized the human immune response against murine monoclonal antibodies (HAMA) in 18 patients following administration of the F(ab')2 fragment of the murine monoclonal antibody OC125. OC125 is directed against the CA125 antigen, present on the surface of many human ovarian cancers. An affinity matrix was used to separate serum into immunoglobulin-containing and immunoglobulin-free fractions. HAMA titer was determined on the immunoglobulin fraction with an OC125 sandwich enzyme-linked immunosorbent assay (ELISA). All patients developed an HAMA response, despite the use of F(ab')2 fragments and small amounts (1-4 mg) of antibody. It may be that the intraperitoneal (i.p.) route provides a more marked HAMA response. Enzyme-linked sandwich immunoassays were also used to determine anti-isotype and anti-idiotype titers. Anti-isotype titers were analyzed with antigen irrelevant, isotype-matched murine antibodies and OC125-HRPO. Anti-idiotypes titers were assessed in a sandwich assay that utilized F(ab')2 and F(ab') fragments of OC125. The anti-isotype response tended to be of low titer and short duration, while the anti-idiotype response was of high titer and remarkably persistent. HAMA interfered in an unpredictable manner with the correct measurement of serum levels of CA125 in an enzyme immunoassay using OC125. Corrected values of CA125 could be obtained by measurement of antigen in the immunoglobulin-free fraction of serum. The response of one patient, who developed a markedly elevated anti-idiotype titer after serial i.v./i.p. injections, was further characterized and found to contain an antibody consistent with an anti-anti-idiotype to the CA125 antigen.
authors.affiliation: Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
authors.forename: V E
authors.initials: VE
authors.lastname: Maher
authors.forename: S J
authors.initials: SJ
authors.lastname: Drukman
authors.forename: R J
authors.initials: RJ
authors.lastname: Kinders
authors.forename: R E
authors.initials: RE
authors.lastname: Hunter
authors.forename: J
authors.initials: J
authors.lastname: Jennings
authors.forename: C
authors.initials: C
authors.lastname: Brigham
authors.forename: S
authors.initials: S
authors.lastname: Stevens
authors.forename: T W
authors.initials: TW
authors.lastname: Griffin
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000917:Antibody Formation; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D012699:Serology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D007140:Immunoglobulin Fab Fragments