A panel of monoclonal antibodies (MABs) that bind preferentially to human lung tumors has been developed that represents an important diagnostic and therapeutic set of reagents. These antibodies are unique in that they have been derived from hybrids that were produced by fusing spleed cells of mice immunized with surgically excised lung tumors (as opposed to tumor cell lines) to a nonsecreting murine myeloma. A characteristic reactivity pattern for each MAb has been established by screening against a large number of normal and neoplastic fresh tissues as well as cultured cell lines. We have established that one of the dominant antigenic determinants recognized by our MAbs is a glycoprotein with a molecular weight of 158,000 (gp158). The gp158 molecule has been detected on adenocarcinomas, alveolar carcinomas and a portion of the large cell tumors of the lung. The gp158 molecule is undetectable in all of the normal human tissues tested; including lung, colon, brain, kidney, heart, stomach, erythrocytes and lymphocytes. These MAbs have been used to establish a simple rapid and sensitive assay that will detect the presence of the gp158 molecule (or other lung tumor associated antigens) on cells or alternatively, antibodies directed against the lung tumor associated antigen(s). We propose to use our panel of MAbs with the former immunoassay to characterize non-small cell lung tumors based upon their reactivity with the library of MAbs. Our ultimate goal will be to correlate the reactivity profile of a tumor with the patient's prognosis and with the most effective therapeutic modality for treatment of this tumor phenotype. We also recognize that our set of MAbs has a significant therapeutic potential. In the course of our work on this project we have been able to prepare cytotoxic drug-containing liposomes (to which we have covalently coupled to the surface anti-idiotype antibody) and to selectively deliver these liposomes in vitro and in vivo to a tumor containing the idiotype on the cell surface. We shall continue to use this tumor model to resolve anticipated problems and to improve upon the efficiency of our drug delivery system. One method by which we may improve upon efficiency is by incorporating the fusion-protein from Sendai virus into the lipid bilayer of the antibody-modified drug-containing liposomes. What we learn from this model will be applied to develop protocols of immunospecific targeting of drug-containing liposomes to human lung tumors.
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