The impact of monoclonal antibodies on the study of human malignant melanoma.
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Biomedical subjects
Publications and source records attributed to K Imai.
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The serologic and molecular characterization of four monoclonal antibodies to human gastric cancer cells and to CEA were described and the immunohistologic patterns of reactions with freshly obtained gastrointestinal tissues were examined. Monoclonal antibody YK004, which was secreted by the hybridoma constructed with the gastric carcinoma cell line KATO III, reacted with an antigenic determinant preferentially expressed on human gastric and colonic carcinoma cells, but it failed to bind any nonmalignant tissues tested except the stomach. Although this antibody reacted with fetal digestive tract tissues, it failed to immunoprecipitate CEA. Monoclonal antibodies YK013 and YK024 prepared in the same manner by immunizing with the gastric carcinoma cell line KATO III reacted with antigenic determinants on CEA, but not on NCA or NCA2. The antigenic profiles recognized by these two antibodies were found to be identical by sequential immunoprecipitation experiments. However, the antigenic determinant recognized by antibody YK013 may be different from that recognized by antibody YK024, since the immunohistologic reactivity patterns in carcinoma tissue sections were clearly different. Monoclonal antibody AS001, which was secreted by the hybridomas constructed with purified CEA as immunogen, immunoprecipitated CEA molecule with a single antigenic structure of 200 Kd, which was different from the antigenic profile detected by two other monoclonal antibodies, YK013 and YK024. The unique distribution of the antigenic determinants recognized by our monoclonal antibodies on cancerous tissues suggests that antibodies might be able to detect the unique determinants of the circulating CEA molecule or CEA-related molecules in the serum of cancer patients.
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Two kinds of the fat-soluble dye, Sudan black and red, were intravenously injected on alternate days into layers aged from 5 to 23 months to study the growth pattern of the ovarian follicle in relation to aging. Results indicated: 1) the length of the rapid growth period showed a tendency to shorten during 5 to 11 months, then to lengthen from 15 to 23 months of age; 2) there was a continuous increase in follicular volume at ovulation with the progress of age; 3) the growth rate (degree of curvature of the growth line calculated in each follicle) was low at 5 months, increased from 8 to 11 months, and remained constant thereafter; 4) during the first year of age, the number of growing follicles in the ovary decreased gradually, whereas the total amount of daily yolk deposition increased. During the second year of age, both the number of growing follicles and total yolk deposition remained constant.
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The I-J and antigen-binding chains with constant region determinant (Ct) that compose an antigen-specific suppressor T cell factor were found on the surface of suppressor T cell hybridomas, serologically and morphologically demonstrated by a fluorescence-activated cell sorter (FACS) and immunoelectron microscopic analyses. Moreover, the surface expression of the I-J and Ct-bearing chains fluctuating with the same kinetics depended entirely upon the cell cycle. The maximum expression of these two chains was observed in the early stage of the M phase, and the minimum in the S phase. Similarly, the magnitude of the suppressor activity was maximal in the late stage of the M phase, and was minimal in the S phase. The results therefore demonstrated that there exists good correlation between the cell surface expression of the I-J and Ct-bearing chains and the magnitude of the suppressor activity produced. The antigen recognition units on suppressor T cell hybridomas have serologically and morphologically been characterized by using radiolabeled antigens or monoclonal antibodies against the I-J or Ct on the antigen-binding molecule. Cell-binding assay and radioautographic analysis demonstrated that the suppressor T cell hybridoma possesses the capacity to bind native antigen in an antigen-specific fashion as does the hybridoma-derived, antigen-specific suppressor factor composed of the I-J and the Ct-bearing chains, indicating that the recognition unit on the cell surface is composed of a structure similar to the factor.
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Monoclonal antibodies to human melanoma associated antigens were reviewed from the viewpoint of a target structure recognized by them. In addition, phase I evaluation of a monoclonal antibody 225.28S in man and fundamental studies of the antibody-cytotoxic agent conjugates in melanoma-bearing nude mice were described.
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The development of hybridoma technology has provided the possibility of preparing unlimited amounts of highly specific and homogeneous monoclonal antibodies thus eliminating many of the disadvantages with conventional antisera and rekindling interest in the application of immunodiagnostic and immunotherapeutic approaches to human cancer. Several reports, including our own of monoclonal antibodies to tumor-associated antigens expressed by solid tumors including gastric, colorectal, lung and other various carcinomas, were reviewed from the viewpoint of tumor markers.