ABSTRACT
Employing as immunogen a short-term passaged, highly pigmented human melanoma cell line, we have produced the murine MoAb 2G10 of the IgG1 isotype. The antibody immunoprecipitated from 35S-methionine and 3H-glucosamine metabolically labeled human melanoma cells with a single-chain glycoprotein of 75 kD molecular weight. No such molecule could be precipitated from murine melanomas. To further investigate the fine specificity of the MoAb, immunochemical and immunohistochemical studies were performed. These studies demonstrated that MoAb 2G10 binds a significant fraction of tyrosinase activity from cell lysates, completely immunodepletes soluble cell extract of T4-tyrosinase molecules, and produces immunostaining patterns superimposable on those obtained with anti-T4-tyrosinase antibodies. Thus, MoAb 2G10 appears to recognize a human-specific determinant carried by either T4-tyrosinase or a closely related molecule. The functional relevance of this epitope remains to be evaluated.
Subject(s)
Antibodies, Monoclonal/immunology , Monophenol Monooxygenase/immunology , Animals , Epitopes , Female , Humans , Immunochemistry , Immunohistochemistry , Mice , Mice, Inbred BALB C , Species SpecificityABSTRACT
The growth and dissemination of Lewis lung carcinoma have been analyzed following treatment of isolated tumor cells or of tumor-bearing animals with monoclonal antibody (MoAb) 135-13C, which recognizes a cell surface tumor-associated protein of 180,000 daltons. The results of this study indicate that MoAb 135-13C binds with high affinity to Lewis lung tumor cells and induces different effects on the primary tumor (20%-25% reduction of tumor weight) and its metastasis (twofold increase of lung nodule formation). Different schedules of MoAb 135-13C administration have shown that these effects are dose- and time-dependent. In particular, the maximum increase in metastasis formation is observed when the MoAb 135-13C is administered at time of systemic tumor dissemination. In vitro preincubation of tumor cells with MoAb prior to their iv injection into normal animals results in a significant increase of pulmonary metastatic nodules.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Lung Neoplasms/therapy , Animals , Antibodies, Monoclonal/immunology , Cell Division , Cell Line , Cell Membrane/immunology , Lung Neoplasms/immunology , Lung Neoplasms/secondary , Mice , Mice, Inbred C57BL , Neoplasm Metastasis/therapySubject(s)
Histocompatibility Antigens Class II/analysis , Kidney/embryology , Thymus Gland/embryology , Adult , Antibodies, Monoclonal/immunology , Female , Fluorescent Antibody Technique , Gestational Age , HLA Antigens/analysis , Histocompatibility Antigens Class II/immunology , Humans , Kidney/immunology , Lung/embryology , Lung/immunology , Lymphocyte Culture Test, Mixed , Pregnancy , Thymus Gland/immunologySubject(s)
Antispermatogenic Agents/pharmacology , Indazoles/pharmacology , Mitochondria/drug effects , Pyrazoles/pharmacology , Testis/drug effects , Animals , Glycolysis/drug effects , Male , Microscopy, Electron , Mitochondria, Liver/drug effects , Oxidative Phosphorylation/drug effects , Oxygen Consumption/drug effects , Rats , Testis/ultrastructureABSTRACT
Analysis of the tissue distribution of human Ia-like antigens has shown that they have a wider distribution than originally reported. Furthermore, the expression of Ia-like antigens may change when cells undergo malignant transformation: for instance, melanoma cells acquire Ia-like antigens, while breast carcinoma cells lose them. Serological and immunochemical analysis of Ia-like antigens with monoclonal antibodies has shown a cellular and molecular heterogeneity of these molecules which had not been previously recognized with conventional allo- and xenoantisera. The functional significance of this heterogeneity is not known. Monoclonal antibodies to human Ia-like antigens cross-react with lymphocytes from other animal species indicating that portions of the molecules have been conserved during evolution. The biological implications of these findings are discussed.
