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Background. Nd2 is a murine monoclonal antibody MoAb) directed against purified mucins of the human pancreatic cancer cell line SW1990. The authors previously reported promising results with Nd2 for immunotargeting pancreatic cancer. However, murine MoAbs induce human anti-mouse antibodies (HAMAs), a serious problem for clinical use. Mouse/human chimeric antibodies may be less immunogenic and therefore reduce the incidence of HAMAs. In this study, the hinding affinity, tumor specificity, biodistribution, and immunoimaging of chimeric Nd2 were evaluated. Methods. The affinity of chimeric Nd2 was evaluated by competition radioimmunoassay and Scatchard analysis using [sup.125]I-chimeric Nd2, [sup.125]I- murine Nd2, and SW1990 mucin. Immunoreactivity against pancreatic cancer tissues was examined histochemically by the avidin-biotin peroxidase complex method. The biodistribution of the MoAbs was examined in athymic nude mice bearing SW1990 xenografts that were administered intravenous [sup.125]I-labeled chimeric or murine Nd2. [sup.111]In-chimeric Nd2 was injected into the same xenograft models, and scintigrams were obtained on day 3. Results. Affinity analysis and immunohistochemical studies showed that chimeric Nd2 had the same affinity to SW1990 mucin and the same specificity for pancreas cancer tissues as murine Nd2. Intravenous administration of [sup.125]I-chimeric Nd2 resulted in a maximum tumor accumulation of 43% of the initial dose/gram of tumor, which was almost identical to the accumulation murine Nd2. Distinct immunoscintigrams of tumors in nude mice were obtained with [sup.111]In-chimeric Nd2. Conclusion. Chimeric Nd2 may have clinical potential in the radioimmunodetection and immunotherapy of pancreatic cancer. Cancer 1995; 75:1545-53.

Background: Mucins are high-molecular-weight glycoproteins produced by both normal and cancer cells. However, in cancer cells, abnormal mucins are synthesized and potentially can be used as markers for the development and progression of certain malignancies. In a previous study, we reported the production of a new monoclonal antibody directed against a mucin antigen termed F1[alpa], an O-linked oligosaccharide similar to sialyl Tn and Thomsen-Friedenreich (T) antigens, that has not been previously detected in human cancers. F1[alpa] is expressed in a high percentage (80.2%; 89/111) of gastric cancers. Purpose: In the present study, we compared the expression of F1[alpa] with that of sialyl Tn and T antigens in human gastric cancer tissues to determine how differences in the expression of these cancer-associated antigens correlated with the biological properties of cancer cells. Methods: A total of 141 cases of gastric cancer were studied. Sections of formalin-fixed, paraffin-embedded tissue were immunostained for F1[alpa], sialyl Tn, and T antigens. The relationship between the expression of these antigens and the patient's clinicopathologic characteristics was studied. The chi-square test (two-sided) was used for statistical analyses. Results: F1[alpa] was expressed in a high percentage of the cases of early to advanced cancers, irrespective of the degree of malignant progression. The rate of expression of sialyl Tn antigen in early carcinoma was low, but it increased significantly as depth of invasion increased P

Background. Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase [delta] and is considered to correlate with the cell's proliferative state. Immunohistochemical methods with a anti-PCNA antibody (PC10) have particular advantages compared with other techniques because of the maintenance of the tissue architecture and simplicity of the methodology. The authors investigated the correlation between the tumor's proliferative activity and progression of gastric carcinoma using immunohistochemical staining with PC10. Methods. One hundred eighty-nine endoscopic biopsy specimens from patients with gastric carcinoma before operation were investigated by immunohistochemical study, using anti-PCNA monoclonal antibody (PC10). The correlation of PCNA labeling index (percentage of positive cells in more than 500 tumor cells) with various clinicopathologic factors and prognosis was studied. Results. The PCNA labeling index became higher as the histologic stage increased. In patients with lymph node metastasis, vascular invasion, liver metastasis, and peritoneal metastasis, the labeling index was significantly higher. In patients with high PCNA labeling index (50% or greater), prognosis was significantly poorer than in those with a low index (less than 50%). The rate of disease recurrence after curative resection was significantly higher in patients with high PCNA grade group. Conclusion. As a result of this study, PCNA labeling index is suggested to be correlated with the depth of invasion, organ metastasis, vascular invasion, and tumor stage and to be effective as a prognostic factor. Cancer 1994; 73:528-33.