An ELISA to determine the biodistribution of human monoclonal antibody in tumor-xenografted SCID mice.
An ELISA technique was developed to assay the distribution of native human monoclonal antibodies (mAbs) in tumor-xenografted SCID mice. This was used in an investigation of its potential as an alternative to the conventional radioisotopic technique for mAb biodistribution assays which would be simpler to implement and might yield results in closer accord with actual mAb activity because it is based on the use and detection of the native mAbs rather than their radioisotope-coupled immunoconjugates. SCID mice bearing xenografted tumors of the human lung adenocarcinoma cell line A549 received injections via the tail vein of four human mAbs that had been obtained from human-mouse heterohybridomas and were known to be reactive with A549. The biodistribution of the mAbs was assayed by the ELISA technique seven days after the mAb injection. The assay yielded tumor/serum ratios for the four reactive mAbs which were in the range of three to six and tumor mAb levels which were in the range of 0.28 to 0.92 %ID/g (percent of injected mAb dose per gram of tumor). The tumor mAb levels were thus lower than the levels commonly found by radioisotopic assay, and further investigation is desirable to determine the cause of the difference. The results indicate that ELISA can provide a simple, practical means of investigating the biodistribution of human mAbs in mice bearing xenografted carcinomas. The application of this procedure would obviate the need for the complex facilities and procedures associated with radioisotopic labelling and assay.
Arai
K
K
Diagnostics R & D Department, Asahi Chemical Industry, Shizuoka, Japan.
Yoshinari
K
K
Matsumoto
K
K
Misaki
H
H
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000032:analysis*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007075:Immunoglobulin M