MoAb B72 Research Articles

Immunoscintigraphy in patients with colorectal, ovarian, and prostate cancer. Results with site‐specific immunoconjugates

Application of monoclonal antibody (MoAb) technology to cancer management is discussed by reviewing the development and clinical evaluation of two MoAb-based immunoscintigraphic agents (111In-satumomab pendetide [OncoScint CR/OV-In] and 111In-CYT-356; Cytogen Corporation, Princeton, NJ). Both agents were prepared using a site-specific MoAb modification method that preserves the immunoreactivity of the radiolabeled immunoconjugate. 111In-satumomab pendetide is an 111In-labeled conjugate of the murine MoAb B72.3, which is directed to TAG-72, an antigen expressed by the majority of adenocarcinomas. By providing information that complements the results of standard radiographic diagnostic modalities, this imaging agent can aid in the treatment of patients with colorectal or ovarian cancer. Immunoscintigraphy with 111In-satumomab pendetide has been shown to assist in medical-surgical management by detecting occult extrahepatic lesions, clarifying equivocal results of other diagnostic imaging tests, and evaluating the extent and resectability of known tumor lesions. 111In-CYT-356 is an 111In-labeled conjugate of the murine MoAb 7E11-C5.3, which is reactive with prostatic carcinoma, benign prostatic hypertrophy, and, to a lesser extent, normal prostatic tissue. Results of preliminary clinical investigations suggest that 111In-CYT-356 immunoscintigraphy can be useful for the presurgical staging of prostatic carcinoma and for the detection of occult distant disease in patients with negative or equivocal results on standard imaging tests. Results with these site-specifically radiolabeled immunconjugates demonstrate the clinical utility of MoAb-based imaging agents in the treatment of patients with solid tumors.

Improved detection of hepatic lesions using MoAb B72.3 and a modified 111In labelling technique in patients with recurrent colon cancer.

In this study, the clinical usefulness of 111In-SCN-Bz-diethylenetriaminepentaacetic acid (DTPA) monoclonal antibody (MoAb) B72.3 in patients with recurrent colorectal carcinoma was evaluated. In previous studies with radiolabelled MoAb B72.3, metastatic liver lesions in patients with colon cancer appeared as areas of either increased (hot lesions) or decreased (cold lesions) activity, and extrahepatic lesions appeared as areas of increased activity. Eleven patients were enrolled in this study, and 12 MoAb imaging study results were correlated with computed tomography/magnetic resonance imaging findings. The improved detection rates (number of hot lesions) in MoAb imaging were 48% (14/29) for hepatic metastases and 60% (6/10) for extrahepatic metastases. This represents a significant improvement in the rate of detection of metastatic disease of the liver in patients with recurrent colon cancer when compared to the rate in previous reports. Seventeen clinically unsuspected hepatic and extrahepatic areas of increased uptake were also identified on MoAb studies, and two of these areas were confirmed as metastatic disease at surgery. The rate of detection of extrahepatic metastases with 111In-SCN-Bz-DTPA MoAb B72.3 was also compared and found to be equal to the detection rates with other radiolabelled immunoconjugates. No major adverse side effects were noted during the administration of the MoAb. Four of nine patients tested had a positive anti-mouse antibody (HAMA) response 3 months after injection. These preliminary data indicate that this 111In-labelled immunoconjugate of MoAb B72.3 demonstrates an improvement in hepatic lesion detection rate than did previously reported preparations in patients with recurrent colon cancer.

Tumor-associated glycoprotein distribution detected by monoclonal antibody B72.3 in salivary neoplasia.

The expression of tumor-associated glycoprotein (TAG-72), an oncofetal mucin-like tumor-associated glycoprotein derived from membrane-enriched fractions of metastatic breast carcinoma, has been detected by monoclonal antibody (MoAb) B72.3 in adenocarcinomas of breast, colon, lung, endometrium, pancreas, and ovary. The authors reported the scope of TAG-72 expression detected by MoAb B72.3 in salivary neoplasia. They examined 96 salivary lesions (53 malignant and 37 benign primary tumors, 2 metastatic carcinomas, and 4 other benign lesions) and 17 normal tissues from parotid glands and found: diffuse TAG-72 expression in 29 of 55 (53%) malignant tumors and 6 of 36 (17%) benign tumors and in no normal tissue; focal TAG-72 expression in 10 of 55 (17%) malignant salivary tumors, 10 of 37 (25%) benign salivary tumors (all benign mixed tumors), and 1 of 17 (6%) histologically normal parotid gland ducts. Any expression of TAG-72, whether diffuse or focal, was found to have a 71% sensitivity for detecting salivary malignant tumors, but an unacceptably low specificity for malignant lesions (57%). Alternatively, if only diffuse TAG-72 expression was regarded as indicative of malignancy, the specificity of diffuse TAG-72 expression was 86%, but sensitivity of detection decreased to 53%. The authors studied a subset of benign and malignant mixed tumors (BMT and MMT) and found that 12 of 15 (80%) MMT diffusely and strongly expressed TAG-72, 2 of 15 MMT (13%) expressed TAG-72 focally, and 1 MMT (7%) was nonreactive. By contrast, most BMT did not express TAG-72; only sparse, focal TAG-72 expression was seen in 10 of 27 (37%) BMT. If diffuse TAG-72 expression is considered indicative of malignancy, its sensitivity and specificity for malignant mixed tumors is 80% and 100%, respectively. The authors suggest that diffuse TAG-72 expression may resolve conflicts in determining whether or not a mixed tumor is malignant.

Enhancement of tumor-associated glycoprotein-72 antigen expression in hormone-related ovarian serous borderline tumors

The immunoreactivity of monoclonal antibody (MoAb) B72.3 with ovarian serous tumors of borderline malignancy from 44 women who were pregnant, were on hormone medication containing a progestin, or were known to be in the secretory phase of the menstrual cycle, was compared with that of similar tumors of 32 patients who were not known to be in any of these three categories. All 76 borderline tumors expressed the tumor-associated glycoprotein (TAG-72) recognized by MoAb B72.3. Striking staining differences (P less than 0.0001) were observed between the hormone-related and the nonhormone-related tumors. Differences were also noticed between the staining of tumors from pregnant patients and that of previous, persistent, or recurrent tumors of the ipsilateral or contralateral ovaries when the same patients were not pregnant. Tumor MoAb B72.3 reactivity increased with progressive gestational age and fell to lower levels at term and during the postpartum period. Although it has been suggested by cell culture studies, enhanced TAG-72 expression in human tumors under hormonal stimulation has not been described before.

High TAG-72 Serum Levels, Defined by MoAb B72.3, in Premenopausal Women with Benign Breast Disease, are associated with Type I Gross Cystic Disease

High TAG-72 Serum Levels, Defined by MoAb B72.3, in Premenopausal Women with Benign Breast Disease, are associated with Type I Gross Cystic Disease

Monoclonal antibody b72.3. an adjunct for evaluation of suspicious aspiration biopsy cytology from the breast

Monoclonal antibody B72.3 (MoAb B72.3) is a potentially valuable diagnostic adjunct when applied to aspiration biopsy cytology (ABC). In this prospective study, its reactivity was tested on the ABC from 25 breast lesions interpreted as suspicious. The stain was applied directly to the Papanicolaou-stained specimen by the avidin-biotin peroxidase methodology at a concentration of 40 micrograms/ml. In 11 aspirates from invasive carcinomas, the reactivity to MoAb B72.3 was strongly positive in nine cases and weakly positive in two. Ten of these tumors were homogeneous or heterogeneous infiltrating lobular neoplasms, tumors causing special diagnostic pitfalls by ABC. The cells from seven of the nine benign lesions were nonreactive, and in two cases from fibrocystic change, weakly reactive. The ABC from five patients with noninvasive carcinomas or atypical lobular hyperplasia showed a variety of responses. The findings indicate that in select circumstances, MoAb B72.3 used in conjunction with clinical and cytologic findings may be a useful diagnostic adjunct.

Peritoneal carcinomatosis: imaging with intraperitoneal injection of I-131-labeled B72.3 monoclonal antibody.

Monoclonal antibody (MoAb) B72.3 is reactive with a variety of carcinomas such as colorectal and ovarian carcinoma and not reactive with a range of normal tissues in adults. Twelve patients, ranging in age from 16 to 63 years, with metastatic colorectal or appendiceal carcinoma were studied by means of radioimmunoscintigraphy after injection of 5-10 mCi (185-370 MBq) of iodine-131-labeled B72.3 immunoglobulin G (IgG). Eight of the 12 patients had positive scans. In three of these patients the MoAb scan depicted tumors that were not found by other means. Positive scans had excellent correlation with surgical findings in seven patients and caused underestimation of the extent of disease in one patient. In one patient the scan was technically inadequate and could not be evaluated. In three patients the scan was negative. No adverse reactions were associated with the infusions.

Monoclonal Antibody B72.3 Reacts with a Core Region Structure of O-Linked Carbohydrates

Monoclonal antibody (moAb) B72.3 appears to be exceptional among the many mouse moAbs reactive with human tumor cells in its degree of tumor specificity. The antigen recognized was characterized as a mucin-like molecule. We report here that B72.3 reacts strongly with ovine submaxillary mucin and that reactivity is abolished by desialylation, suggesting that the determinant recognized is the disaccharide N-acetylneuraminic acid alpha (2----6)-N-acetylgalactosamine, linked to serine or threonine, which might be designated sialylated Tn. A variety of human mucin preparations, including human salivary mucins, and other glycoproteins containing O-linked or N-linked carbohydrates were nonreactive. The data suggest that the determinant recognized is a core structure which is normally not exposed due to chain elongation at C-3 of the N-acetylgalactosamine, which appears to be less frequent in carcinoma cells than in normal cells.

Tumor-Associated Glycoprotein (TAG-72) in Ovarian Carcinomas Defined by Monoclonal Antibody 872.3

Murine IgG1 monoclonal antibody (MoAb) B72.3, reactive with a high molecular weight glycoprotein complex [designated tumor-associated glycoprotein-72 (TAG-72)] was shown, with the use of the avidin-biotin-complex-immunoperoxidase technique and surgically resected tissues, to be reactive with a variety of histologic tumor types. TAG-72 is expressed in at least 5% (and up to 100%) of the malignant epithelial cells in 77% (n = 52) of human primary cancers and 71% (n = 31) of metastatic ovarian cancers of the common "epithelia" histologic category. Of these, several histologic types, including serous and mucinous cystadenocarcinomas, undifferentiated carcinomas, and less common types of ovarian carcinoma, were all shown to express TAG-72. In contrast, normal ovarian tissues and 26 of 27 benign ovarian tumors of various histologic types failed to express similar levels of TAG-72. Of interest is the 1 benign tumor that demonstrated unusual glandular complexity, as well as 3 tumors designated as borderline malignancy, that contained elevated TAG-72 expression. MoAb B72.3 also was used successfully to detect ovarian carcinoma cells in 28 cytologic preparations of human serous effusions and peritoneal washings. The reactivity of MoAb B72.3 was shown to be distinct from that of MoAb OC125 and an anti-CEA MoAb B1.1. The potential applications of MoAb B72.3 in the study of human ovarian cancer cell populations, as well as in several aspects of the management of human ovarian cancer, are discussed.