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Background. Interleukin-6 (IL-6) is a multifunctional cytokine that can be produced by human ovarian cancer cells. Elevated IL-6 levels have been found in the serum and ascites of patients with ovarian cancer, but its role in this disease has not been clearly established. Methods. The authors studied the relationship between IL-6 levels in serum and ascites, various tumor parameters, and survival in 70 patients with newly diagnosed, untreated epithelial ovarian cancer. Ascites and serum specimens were obtained at the time of initial surgery, and IL-6 levels were determined using the B9 bioassay. Results. All patients underwent platinum-based chemotherapy after initial surgery. The median age of the group was 62 years (range, 28-87 years), and the median follow-up time was 13 months (range, 12-59 months). Significantly higher IL-6 levels were detected in patients' ascites (median, 49,612 pg/ml [range,

Background. Colon-specific antigen-p is a tumor-associated antigen present in approximately 60% of colorectal cancers. Preclinical studies have shown that the murine monoclonal antibody Mu-9 has excellent tumor-targeting abilities; therefore, clinical studies were initiated. Methods. The immunoglobulin G and [F(ab').sub.2] were radiolabeled with [I.sup.131] and administered to 13 and 12 patients, respectively, with advanced gastrointestinal cancer (colon, rectal, and pancreatic) for radioimmunodetection or radioimmunotherapy. Results. Even in patients with highly elevated carcinoembryonic antigen levels, only one patient showed appreciable complexation of the labeled antibody, suggesting the epitope may not be highly expressed in the blood. Fifty percent of [I-Mu-9.sup.131] immunoglobulin G was cleared from the blood within 41 [+ or -] 13 hours, while it took only 19 [+ or -] 8 hours for the same amount [I.sup.131]-[F(ab').sub.2] to be cleared from the blood. Lesion detection in the abdomen, liver, and pelvis was greater than 90% for either the immunoglobulin G or [F(ab').sub.2]. The dose absorbed by the normal organs, except the kidneys, was two- to threefold less for the [F(ab').sub.2] than for the whole immunoglobulin G. The dose to the kidneys was similar for both forms of immunoglobulin. The average tumor dose for [I-Mu-9.sup.131] immunoglobolin G was 13.9 [+ or -] 11.0 cGy/mCi, and for [I-F(ab').sub.2.sup.131] was 4.9 [+ or -] 2.9. Tumor/red marrow dose ratios for the whole immunoglobulin G were 4.3 [+ or -] 3.0, compared to 3.3 [+ or -] 1.9 for the [F(ab').sub.2], suggesting the therapeutic window for the two forms of immunoglobulin may be similar. Eight of nine patients given the whole immunoglobulin G developed highly elevated levels of human anti-mouse antibody, whereas lower values were observed in five of seven patients given the [F(ab').sub.2]. Conclusions. These initial results support the need for further evaluation of Mu-9 immunoglobulin G and [F(ab').sub.2] for targeting gastrointestinal cancer for radioimmunotherapy. Cancer 1994, 73:864-77.

Background. The authors previously reported that an anticarcinoembryonic antigen antibody against a carcinoembryonic antigen (CEA)-specific epitope is preferred for clinical investigations. They developed a second generation, CEA-specific murine monoclonal antibody (MoAb), MN-14 (IMMU-14), that has a tenfold higher affinity. This report summarizes the initial clinical experience with the new MoAb. Methods. MN-14 immunoglobulin G (IgG) (0.5-6.0 mg) was labeled with radioactive iodine ([I.sup.131] (5-80 mCi) and injected into 22 patients with cancer. External scintigraphy was used to determine targeting in patients with low and highly elevated plasma CEA. Quantitative external scintigraphy methods were used to determine organ and tumor clearance rates and absorbed radiation doses. Targeting data were correlated with several factors, including MoAb protein dose, plasma CEA, and relative tumor burden. Results. Despite more than 80% complexation with plasma CEA of more than 500 ng/ml, all known tumor sites were disclosed by external scintigraphy. The overall sensitivity of tumor targeting on a lesion basis was 89%. The residence time in the blood was predicted by body weight (P = 0.05) and the log of plasma CEA (P = 0.043). The absorbed dose to the red marrow and total body could be predicted by the body weight of the patient, but no other factor contributed significantly to the clearance rate or absorbed dose to the organs. Individual tumors received an average dose of 9.3 [+ or -] 6.4 cGy/mCi. The absorbed dose to the tumors was negatively correlated to the weight of the tumor, and the percent uptake in the tumor was positively correlated to the estimated total tumor burden. Patients injected with approximately 5 mg of MN-14 IgG were more likely to have anti-mouse antibodies (HAMA) develop than were patients who were injected with less MoAb. Conclusions. These results suggest that MN-14 targets tumors effectively, even in the presence of elevated circulating CEA. Additional studies are necessary to determine if an advantage for the higher affinity MN-14 MoAb, compared with the lower affinity NP-4 MoAb, can be appreciated clinically. Cancer 1993; 71:2082-96.