Monoclonal antibodies that demonstrate specificity for several types of human lung cancer.

Abstract

Monoclonal antibodies with selectivity for human lung cancer were produced by immunizing BALB/c mice with an established line of human small cell lung cancer (NCI-H69) and fusing the mouse spleen cells to mouse myeloma line X63-Ag8.653. The resulting hybrid cells were initially screened' by immunoautoradiography for production of antibodies that would react with NCI-H69 and another small cell lung cancer line (NCI-H128) but not its autologous B-lymphoblastoid line (NCI-H128BL). Stable monoclonal antibody-producing lines were isolated by repeated cloning. Three independently derived monoclonal antibodies, designated 525A5, 534F8, and 538F12, were found to react with three of the major types of human lung cancer (small cell, adenocarcinoma, and squamous carcinoma). They did not react with bronchioloalveolar and large cell lung cancers, myeloma, lymphomas, leukemias, osteogeneic sarcoma, mesothelioma, hypernephroma, malignant melanoma, simian virus 40-transformed human fetal lung cells, skin fibroblast lines, human B-lymphoblastoid lines, human erythrocytes, and rodent cells. Interestingly, these antibodies also bound to three out ofthree human neuroblastomas and two out of three breast cancers but failed to react with mouse neuroblastoma and rat pheochromocytoma. The monoclonal antibodies reacted with human small cell lung cancer tumors obtained at autopsy, but had insignificant reactions with normal human lung, liver, spleen, and skeletal muscle. We conclude that monoclonal antibodies have been generated that react with common antigenic determinants expressed on several human lung cancer types, neuroblastoma, and some breast cancers, but are not detectable by our current assays on a variety of other human tumors or normal adult human tissues. Such antibodies are of potential clinical and biological importance.Antibodies with sufficient specificity for human lung cancer are potentially important diagnostic and therapeutic tools. Several groups have prepared polyclonal antibodies with potential specificity for lung cancer by using standard immunologic methods (1-8). The development of somatic cell hybrid technology for the production of monoclonal antibodies (9) offers a different approach, and several monoclonal antibodies have been reported with various degrees of specificity to a variety of human neoplasms (10-17). In this report, we describe the use of this technology to prepare antibodies with specificity for human lung cancer. As a first approach, we wanted to make monoclonal antibodies that react selectively with lung tumors but not with autologous histocompatibility antigens. Thus, we immunized mice with a line of small cell lung cancer (SCLC) and screened the resultant hybrid cell antibodies for reactivity against the immunizing line and another SCLC line and for lack ofreactivity with an autologous B-lymphoblastoid cell line. Using this strategy, we have isolated, cloned, and developed stable hybrid cell lines producing antibodies that detect determinants expressed on human SCLC, and to a lesser ...

An adherent subline of a unique small-cell lung cancer cell line downregulates antigens of the neural cell adhesion molecule.

“…Like most SCLC-v lines, H446 cells do not express L-dopa decarboxylase or bombesin-like immunoreactivity (8). The classic SCLC lines H209 and H146, the SCLC-v line N417 and the NSCLC lines HI 57, H125, and H522 were used for comparative studies and have been previously described (9). Two unusual SCLC lines, H1607 and H196-B, which form adherent monolayers in vitro, were also used.…”

Monoclonal antibodies against two human lung carcinoma cell lines

“…The target antigens recognized by these antibodies again appear to be present at a higher density on most (Kasai et al, 1981;Cuttitta et al, 1981). To this extent, reagents of the type generated in this study offer potentially a productive means of delineating the complex antigenic profiles of human lung cancer.…”

“…Sikora & Wright (1981) generated antibodies from interspecies hybrids of hilar and bronchial lymph nodes, with rat or mouse myeloma cells, which were preferentially reactive with lung tumour cell membranes, in comparison with those of normal lung tissue. Other investigators, using established cell lines as immunogens, have developed intraspecies hybrids producing antibodies recognizing antigens of variable distribution on lung and other cancer cells (Kasai et al, 1981;Cuttitta et al, 1981).…”

Radioimmunoimaging of Non-Small Cell Lung Cancer with111In- and99MTc-Labeled Monoclonal Anti-Cea-Antibodies

“…Most non-small cell lung cancers react with CEA immunohistochemically (38,(41)(42)(43)(44)(45)(46)(47)(48). With this antibody, intense immunohistochemical staining is obtained both in squamous cell and adenomatous cancer cells (Fig.…”