Generation of bispecific monoclonal antibodies for two phase radioimmunotherapy

• Published in: British journal of cancer Vol. 63; no. 5; pp. 681 - 686
• Main Authors: BOSSLET, K, STEINSTRAESSER, A, HERMENTIN, P, KUHLMANN, L, BRUYNCK, A, MAGERSTAEDT, M, SEEMANN, G, SCHWARZ, A, SEDLACEK, H. H
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.1991
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal - therapeutic use; Antineoplastic agents; Biological and medical sciences; Colonic Neoplasms - metabolism; Colonic Neoplasms - radiotherapy; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Humans; Injections, Intravenous; Medical sciences; Mice; Mice, Nude; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - radiotherapy; Pentetic Acid - metabolism; Pentetic Acid - therapeutic use; Pharmacology. Drug treatments; Tumor Cells, Cultured; Yttrium Radioisotopes - metabolism; Yttrium Radioisotopes - therapeutic use; Antineoplastic agent; Human; Hybridoma; Monoclonal antibody; Radioisotope; Malignant tumor; Carcinoembryonic antigen; Mucin; Immunotherapy; Preparation; Chelating agent; Immunoradiotherapy; Isolation; Combined treatment; Colon
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1991.155

A two phase radioimmunotherapy based on bispecific MAbs in which one arm recognises a tumour antigen and the other a radiolabelled chelate, may prove more effective in the treatment of carcinomas than currently available immunotherapies. To establish this system we first showed that penetration into human carcinoma xenografts as well as long term retention of intact MAb outside the carcinoma cells can be obtained. Epitope saturation was not obtained however, despite the large MAb doses injected i.v. for 10 days. We then generated hybridomas producing high avidity anti-metal chelate MAbs (anti-DTPA-Y). These hybridomas were fused with hybridomas producing MAbs against CEA or GIT-mucin, and stable bispecific MAb producing quadromas were obtained. For the anti-GIT-mucin x anti-chelate MAb a purification procedure based on double anti-idiotype affinity chromatography was shown to result in greater than 95% pure bispecific immunoreactive MAb. Comparative in vivo stability studies profiled DTPA-Y as the chelate of choice for in vivo application.