Antitumor monoclonal antibodies for radioimmunodetection of tumors and drug targeting

Abstract

Developments in hybridoma technology leading to the production of monoclonal antibodies recognizing tumor-associated antigens are providing new approaches for the radioimmunodetection of, and drug targeting to, metastases. These developments are illustrated in a series of studies on the in vivo localization of an antihuman-osteogenic sarcoma monoclonal antibody (791T/36) in human tumor xenografts maintained in immunodeprived mice. 131I-labelled 791T/36 antibody localized specifically in osteogenic sarcomas but not in xenografts of other tumors, such as bladder carcinoma T24, which do not express the antigen identified by this antibody. Developing from these studies, various parameters influencing antibody localization in tumors were examined including the kinetics of antibody uptake, the relationship between tumor size and antibody binding, and the site of antibody deposition. This provides a basis for considering the potential of antitumor monoclonal antibodies for targeting antitumor agents. Of particular importance here is the observation that antibody is principally located at the periphery of tumors since this will influence the population of cells within a tumor which can be attacked by antibody-drug or antibody-toxin conjugates. Experiments with human tumor xenografts demonstrate tumor localization of radioisotope-labelled 791T/36 monoclonal antibody. Tumor localization by external gamma camera imaging of osteogenic sarcoma xenograft-bearing mice was also demonstrated. These studies illustrate the potential of antitumor monoclonal antibodies for imaging primary and metastatic tumors. This approach is further emphasized by the radioimmunodetection of primary and metastatic colorectal carcinomas.

Human parathyroid antigen: characterization and localization with monoclonal antibodies.

“…Since the grafts are dependent on a parasitic blood supply until neovascularization occurs, they often contain some central areas of necrosis and fibrosis, with the clusters of viable parathyroid cells located peripherally. A similar histological pattern has been noted in other radiolocalization studies in tumor models (4,30).…”

“…Numerous investigators used monoclonal antibodies developed against human tumor cells to radioimage tumor xenografts, usually in nude mouse model systems (2)(3)(4)(5)(6)(7)(8)(9). However, most of these studies focused on poorly defined and often nonspecific tumor-associated antigens.…”

Improved Cancer Therapy and Molecular Imaging with Multivalent, Multispecific Antibodies

“…[4][5][6][7][8] By the 1980s, new chemistries for radiolabeling proteins were being developed that greatly expanded the possibilities for a variety of imaging and therapeutic radionuclides, and, importantly, murine monoclonal antibodies became available. [9][10][11][12][13][14][15][16][17][18][19] Hybridoma technology ultimately ushered in a new age of molecular engineering that has revolutionized the applications of antibodies and biologics alike. Murine monoclonal antibodies were chimerized and then humanized to reduce immunogenicity.…”

Radioimmunotherapy of human hepatocellular carcinoma xenografts with 131I-labelled antiferritin antibody

“…For example, tumour growth was accompanied by a linear uptake of 1251-labelled monoclonal antibody (MoAb) in a murine human tumour system while the antigen of that model was not detected in the circulation (Baldwin & Pimm, 1983). Enlargement of tumours was accompanied by a measurable decrease in tumour concentration of "3'I-MoAb.…”