Endocytosis Of The Antigastric Cancer Monoclonal Antibodies And Their Immunoconjugates

At the turn of the century, Paul Ehrlich planted the seed of a conceptual modality of cancer treatment using vehicles (viz., antibodies) for targeting cytotoxic agents specifically to cancer cells. Yet, it is predominantly with the introduction of hybridoma technology making possible the mass-scale generation of antitumor antibodies that his 'magic bullet ' notion has become a realistic proposition. During the last decade, the concept of targeted delivery has become a subject of both intensive and extensive investigation. However, in general the clinical results, while somewhat encouraging, have not lived up to the initial expectations of the early perceived potential. The reasons for this dismal inefficiency are now being understood. As a matter of fact, in antibody targeting one is expecting more complexities than ever envisaged, among which the role of endocytosis has only recently been recognized and explored.Upon perusal of the data identified between 1975 and 1991 through a computer search using MEDLINE, we found that reports on antibody endocytosis were largely derived from blood-forming cell lines, and, to a lesser extent, from solid tumors. Nonetheless, the evidence accumulated all seems to indicate that endocytosis of targeting molecules correlates directly with the targeting efficiency. On the other hand, data presently available in the literature also demonstrate that the divergences of antibody endocytosis in tumor cells are for the time being unpredictable. It is therefore indispensable to determining the endocytosis properties of each given antibody under targeting investigation.As far as we know, few studies to date have been performed concerning the endocytosis of antigastric cancer monoclonal antibodes and their immunoconjugates. Recently, a battery of antigastric cancer monoclonal antibodies have been produced in our laboratory. Accordingly, there has been a strong need to identify their endocytosis properties with a special focus on the intracellular trafficking details and on their possible implications for the future clinical applications. Standing on the background thereinbefore , we conducted the following experiments:...