title: Development of an enzyme-linked immunosorbent assay system to determine the presence of antibodies specific for taxane structures.
abstract: Taxanes, which are widely used in treatment of numerous cancer types, are well-known to induce hypersensitivity reactions (HSR), especially in the case of paclitaxel. Although the cause of the HSR is commonly thought to be a non-immunological direct effect of the diluent which is used to dissolve paclitaxel, some reports suggest the possibility of the presence of an immunological reaction to the common taxane structure. The aim of this study was to establish a method to determine the presence of anti-taxane antibodies in body fluids of patients who have previously received paclitaxel, in order to estimate the risk of the occurrence of HSR to other taxane compounds, such as docetaxel. To prepare an enzyme-linked immunosorbent assay (ELISA) plate for determining taxanes, 10-deacetylbaccatin III (DAB) was first succinylated by use of dimethylaminopyridine and succinic anhydride in dried pyridine. After the succinylation reaction, three different products were obtained, and these were confirmed as 7-succinoyl DAB (7-DAB), 10-succinoyl DAB (10-DAB), and 7,10-disuccinoyl DAB (7,10-DAB) by (1)H-NMR analysis. Each of these three products was conjugated with bovine serum albumin (BSA), and adsorbed on an ELISA plate. By using a commercially available anti-taxane monoclonal antibody as a model antibody, the detection limit of the anti-taxane antibodies on the 7-DAB-BSA-, 10-DAB-BSA-, and 7,10-DAB-BSA-conjugated ELISA plate was estimated as 0.3, 1 and 10 ng/ml, respectively. The ELISA system established in this study may therefore be useful for estimating the risk of HSR to taxanes in a patient prior to the use of these drugs.
authors.affiliation: Department of Disease Analysis, Faculty of Pharmaceutical Sciences, Toho University, Miyama, Funabashi, Chiba, Japan. satoshi@phar.toho-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Muto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kouyama
authors.forename: Yuusaku
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuno
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ishii
authors.forename: Toru
authors.initials: T
authors.lastname: Masaka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawashima
authors.forename: Koji
authors.initials: K
authors.lastname: Shirai
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005658:Fungi / Q000737:chemistry / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D008517:Phytotherapy / Q000009:adverse effects*; D012307:Risk Factors; D043823:Taxoids / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D020946:Taxus / Q000737:chemistry / Q000276:immunology / Q000382:microbiology
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D017239:Paclitaxel