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Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 217 records · Page 12Linked to original sources
PubMed1986

Differential diagnosis between mesotheliomas and metastatic adenocarcinomas using monoclonal antibodies against gastrointestinal carcinoma antigen and stage-specific embryonic antigen.

Monoclonal antibodies made against gastrointestinal carcinoma antigen (GICA) and stage specific embryonic antigen (SSEA) were evaluated for their ability to distinguish normal mesothelial cells present in pleural and peritoneal fluids from adenocarcinoma cells in tissue and cytology specimens. The presence of GICA was documented in a high percentage of adenocarcinomas from the gastrointestinal tract (75/98) and in 52% of pulmonary (15/29) and 29% of ovarian (6/21) adenocarcinomas. GICA was found infrequently in breast carcinoma (1/18) and not in mesotheliomas (0/16). A similar pattern of GICA expression was seen in malignant effusions from adenocarcinomas (18/47) and mesotheliomas (0/6). SSEA was found in a high percentage of adenocarcinomas derived from the gastrointestinal tract (47/56) and the lung (26/29). SSEA was detected in breast carcinoma (8/15) more often than GICA. SSEA was detected rarely in mesotheliomas (1/16). Reactivities for epithelial membrane antigen, keratin, carcinoembryonic antigen, GICA and SSEA in adenocarcinoma and mesotheliomas were compared.

Adenocarcinoma↗
PubMed1986

Expression of melanoma-associated antigens by normal and neurofibroma Schwann cells.

The cell surface antigen distribution on traumatic neuroma Schwann cells and neurofibroma Schwann-like cells was characterized using monoclonal antibodies that define melanoma-associated antigens. Immunofluorescence staining of cultured cells, immunoprecipitation of radioiodinated antigens from cells placed in short-term cultures, and immunoperoxidase staining of frozen tissue sections revealed most of the melanoma-associated antigens tested on traumatic neuroma and neurofibroma Schwann cells and on fetal and adult femoral nerve. The cross-reactivity of the antibodies with neural cells may reflect the common neural crest embryological origin of Schwann cells and melanocytes. Cell sorter analysis of neurofibroma cells using a monoclonal antibody directed against the melanoma nerve growth factor receptor resulted in cell cultures highly enriched for Schwann-like cells which may bear the genetic defect responsible for neurofibromatosis. The antigen detected by this monoclonal antibody is the neurofibroma nerve growth factor receptor and the antibody was a potent inhibitor of nerve growth factor binding to neurofibroma cells.

Antibodies, Monoclonal↗
PubMed1986

Human cutaneous nevi transplanted onto nude mice: a model for the study of the lesional steps in tumor progression.

Normal human cutaneous nevi were transplanted to the skin of nude mice and some of the grafts were treated topically with 7,12-dimethylbenz[a]anthracene (DMBA, 1.6 mumol weekly). Histologically proven human skin was present in 22 grafts. In the 9 untreated control grafts, the tendency of nevic cells to form nests and the number of nevomelanocytes decreased with time; the melanocytic cells showed no signs of hypertrophy or atypia. In most of the 14 specimens treated with DMBA, the nevomelanocytes showed distinct signs of hypertrophy. The cells were enlarged and often dendritic and were filled with melanin granules for which the transfer to keratinocytes appeared to be blocked. The nevomelanocytes of 4 of the 9 specimens treated with DMBA for greater than or equal to 82 days (9-16 DMBA applications), showed atypical enlarged nuclei with mitotic figures. Since atypia is one criterion for identifying precursors of transformed cells, the model of human nevi grafted onto nude mouse skin may be useful for studying the various steps involved in the progression of benign melanocytic nevi to malignant melanoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17-1A administration in patients with gastrointestinal carcinoma.

Twenty-seven patients with metastatic adenocarcinoma of the colon or pancreas were treated with 400mg of monoclonal antibody 17-1A. This antibody, which binds to a cell surface glycoprotein moiety preferentially expressed by adenocarcinomas of the rectum, colon, pancreas, and stomach, is postulated to induce antibody-dependent monocyte cytotoxicity (ADMC) as a mechanism of tumor lysis. Therapy was preceded by four days of gamma interferon infusions, with the intent of activating peripheral blood monocytes, enhancing monocyte Fc receptor expression and increasing the likelihood of tumor lysis as reflected by enhanced ADMC directed against a colon carcinoma cell line (SW1116) which expresses 17-1A's target antigen. In this Phase I study patients were treated daily at one of the following gamma interferon dose levels (X 10(6) U/M2/day): 0.001, 0.01, 0.1, 1.0, 10.0, 40.0, 60.0, 80.0. Addition of 100 U/ml of rIFN-gamma in vitro to monocytes isolated from normal controls or from patients prior to treatment significantly enhanced monocyte Fc receptor expression and ADMC. in vitro tumor cell killing by monocytes and monoclonal antibody was enhanced by treatment with low doses of rIFN-gamma, while treatment with high doses of rIFN-gamma did not enhance ADMC. No objective clinical responses were noted, although serum tumor markers dropped transiently in 36% of the treated patients. Seven of 11 assayed patients developed human anti-idiotype antibodies. With better scheduling of rIFN- and 17-1A we hope to duplicate optimal in vitro conditions for antibody-mediated cytotoxicity, hopefully enhancing in vivo antibody mediated tumor lysis.

Adenocarcinoma↗
PubMed1986

Multiparameter evaluation of the expression in situ of normal and tumor-associated antigens in human colorectal carcinoma.

The immunoreactivity of a panel of monoclonal antibodies (MoAb) was studied in a series of patients with colorectal carcinomas to test the association of antigen expression with other parameters such as histopathologic stage, differentiation, and clinical outcome. Low-level binding to normal tissue and high-level binding to malignant tissue were observed with MoAb defining, respectively, a gastrointestinal cancer antigen (GICA), Leb (distal colon only), A, H type 2 antigen, X-like antigen, and the 200-kilodalton (Kd) protein of carcinoembryonic antigen (CEA). The degree of histologic differentiation correlated with the expression of Lea antigen, A, and Y haptens, whereas a progressive loss of these antigens coincided with loss of differentiation. Two undifferentiated carcinomas expressed only two, H type 2 antigen and a highly glycosylated protein of 20-50 Kd, of the 14 antigens investigated. An interesting, but not significant, association between Leb antigen expression and more extensive disease was found: Whereas 71% of Dukes C tumors were positive for Leb, only 48% of patients with Dukes A and B2 tumors showed the presence of Leb antigen. On the other hand, the presence of B72.3-defined antigen is significantly associated with an earlier stage of disease. Chi-square tests to assess the association of antigen positivity with disease recurrence indicated a significant binding association with tumor recurrence over a broad range of percent positive cells for two MoAb defining different determinants of GICA. Similar associations, but over a narrow range of positive cells, were found for H type 2 antigen and the 200-Kd protein of CEA.

ABO Blood-Group System↗
PubMed1986

Anti-idiotypic antibodies to monoclonal antibody CO17-1A.

Anti-idiotypic antibodies (Ab2) raised during the course of monoclonal antibody (MAb) therapy against anti-colorectal carcinoma (CRC) MAb CO17-1A were characterized in 142 patients with carcinomas of the colon, rectum or pancreas. Ab2 comprised between 21 and 80% of the total human anti-mouse IgG antibodies in various patients, and up to 42 micrograms of Ab2 were isolated per ml serum. In one patient significant levels of Ab2 could be detected for greater than 770 days. Between 20 and 70% of Ab2 in various patients bound to the combining site of MAb CO17-1A and may therefore bear the internal image of the 17-1A tumor antigen. Furthermore, Ab2 isolated from different patients showed considerable cross-reactivities. A beneficial role of the Ab2 responses in the cancer patients who improved clinically following MAb immunotherapy is discussed in light of induction by Ab2 of anti-anti-idiotypic antibodies (Ab3) with tumor-binding activities.

Animals↗
PubMed1986

Treatment of advanced measurable or evaluable pancreatic carcinoma with 17-1A murine monoclonal antibody alone or in combination with 5-fluorouracil, adriamycin and mitomycin (FAM).

Between 1/85 and 3/86, 16 patients with advanced measurable or evaluable pancreatic carcinoma were treated with mouse monoclonal antibody consisting of a single dose of 400 mg 17-1A immunoglobulin given intravenously. None of the eight patients who received monoclonal antibody alone had any subjective or objective benefit. Two of the eight patients who received a combination of monoclonal antibody and 5-fluorouracil, adriamycin and mitomycin (F.A.M.) chemotherapy had clinically useful partial responses lasting 11 months and 7 months respectively. One of these patients, whose initial treatment consisted of an 8-week cycle of F.A.M. chemotherapy, had progressive deterioration as evidenced by weight loss and persistent abnormality of his CT scan, and then achieved a partial response following a single injection of monoclonal antibody while chemotherapy was continued. His response lasted 11 months. There was no toxicity associated with the administration of monoclonal antibody, and the F.A.M. chemotherapy was well-tolerated with moderate and acceptable hematologic toxicity and mild gastrointestinal side effects. There were no treatment-related deaths.

Adult↗
PubMed1986

Clinical trial of Wistar Institute 17-1A monoclonal antibody in patients with advanced gastrointestinal adenocarcinoma: a preliminary report.

Immunotherapy using monoclonal antibody 17-1A has been performed on 22 patients with metastatic gastrointestinal cancer. Criteria for treatment included objective evidence of advanced colon, gastric, or pancreatic cancer (positive CAT scan or x-rays, elevated tumor markers, and/or abnormal liver function tests). The tumor tissue was antigenically positive in all cases. Performance status ranged from 50 to 100%. No adverse reactions were noted. Of the 22 cases treated, 4 (18%) have died, none have rapidly progressive disease, 4 (18%) have slowly progressive disease, 10 (45%) are considered stable with disease, and none are considered partial or complete responses. It is too early to classify the response in 4 cases. In 6 of 8 patients where anti-idiotypic data was available, death or progressive disease was correlated to negative anti-idiotypic response, and clinical stability to a positive anti-idiotypic response. In the patients considered to be stable, the percent change from pre-treatment serum 19-9 concentrations to current values ranged from -10% to +353%. In the patients who have died or have been classified as slowly progressive the serum 19-9 changes ranged from +13% to +707%.

Adenocarcinoma↗
PubMed1986

Detection of murine immunoglobulin in human tissues following therapeutic infusion of monoclonal antibody.

A class switch variant of hybridoma CO19-9 secreting IgG2a antibodies was shown to have the same immunoperoxidase binding pattern in human tissue as the IgG1 antibody secreted by the parental hybridoma. The IP tissue binding of GA73.3 and 17-1A monoclonal antibodies which have been suggested to bind to structurally related antigens were compared; although quite similar in distribution, some differences were noted. GA73.3 bound to 12/12 colon carcinomas compared to 17-1A which reacted with 11/12 tumors. In several cases, the percentage of cells reactive with GA73.3 (90-100%) exceeded those reactive with 17-1A (10-25%). Additionally, the intensity of reactivity for GA73.3 was consistently greater than that seen with 17-1A. The detection of murine antibody bound to human tissues following therapeutic infusion of 19-9 IgG2a or GA73.3 differed. Detection of antibody-antigen complexes was seen less often in patients who had received 19-9 IgG2a (2/6) than in patients who had received GA73.3 (5/5). Additionally, the presence of murine immunoglobulin was seen only in the extracellular mucin of the patients receiving 19-9 IgG2a, whereas strong cellular binding of murine immunoglobulin was noted following infusion with GA73.3.

Animals↗
PubMed1986

Trial of therapy with monoclonal antibody 17-1A in pancreatic carcinoma: preliminary results.

Monoclonal antibody 17-1A was administered to 25 patients with advanced unresectable carcinoma of the pancreas. Ten patients received 17-1A alone in 400 mg doses delivered intravenously, while 15 patients received 400 mg 17-1A absorbed on to autologous peripheral blood mononuclear cells collected by leukapheresis (usual yield greater than 10(9) cells). No toxicity was observed. Twenty-three patients developed circulating anti-murine immunoglobulin within three weeks of treatment, and 11 patients developed circulating anti-idiotypic immunoglobulin. Four out of 19 clinically evaluable patients (21%) showed objective regressions of tumor. Response did not correlate with the presence or absence of anti-idiotypic antibody and did not correlate with the method of treatment with 17-1A alone or 17-1A and mononuclear cells, at the time of current analysis.

Antibodies, Monoclonal↗
PubMed1986

Treatment of patients with metastasizing colo-rectal carcinoma with mouse monoclonal antibodies (Moab 17-1A): a progress report.

Eight patients with metastasizing colo-rectal carcinoma have been treated with Moab 17-1A. Before infusion the antibodies were incubated in vitro with isolated autologous blood mononuclear cells (AMC) enriched for monocytes/macrophages. Treatment was given in repeated courses (2-4 times) up to a maximum amount of 1000 mg Moab 17-1A. Two patients had an objective tumor reduction. In further four patients a period of stable disease varying between 3-6 months on was observed. Therapy was well tolerated. Out of 24 treatment courses only on one occasion an anaphylactoid reaction occurred at the third infusion. All patients developed anti-mouse antibodies of IgG and IgM class with increasing levels during the course of therapy. Repeated tumor biopsies and immunohistochemical analyses showed no antigenic modulation, a weak staining for mouse IgG, no deposits of complement components but no obvious increases in the number of cells infiltrating the tumors 24 h after infusion of antibody-armed AMC.

Adult↗
PubMed1986

Identification and characterization of the CO17-1A carcinoma-associated antigen.

The cell surface antigen defined by monoclonal antibody CO17-1A is sensitive to proteinase K but not to neuraminidase digestion. Immunoprecipitation of two polypeptide chains of 30 and 40 kDa using large amounts of CO17-1A antibody confirmed that the CO17-1A antigen is a protein. The requirement for large quantities of CO17-1A antibody may relate to the binding properties of this antibody, as bivalent but not monovalent (Fab) forms of the antibody bind effectively to carcinoma cells. The 30 kDa form of the CO17-1A antigen was purified by immunoaffinity chromatography using GA733, another monoclonal antibody that recognizes the CO17-1A antigen. Treatment of purified antigen with endoglycosidase F revealed a 25 kDa and a 28 kDa species, demonstrating that the antigen has at least two N-linked oligosaccharide chains. Protease treatment of the purified antigen revealed a 26 kDa protease-resistant polypeptide.

Antibodies, Monoclonal↗
PubMed1986

Improved radioimmunoimaging of human tumor xenografts by a mixture of monoclonal antibody F(ab')2 fragments.

F(ab')2 fragments of monoclonal antibodies (MAbs) GA 73-3 and CO 29.11, with specific binding reactivity in vitro to human tumors of the gastrointestinal tract, were radioiodinated and injected into nude mice bearing human colon carcinoma xenografts. Fragments of both MAbs preferentially localized in tumor tissue compared with normal mouse tissue, as determined by differential tissue counting of radioactivity. The fragments localized specifically only in those tumors to which they bind in vitro and not in unrelated tumors. Radiolabeled fragments of an anti-hepatitis virus MAb did not localize in the tumors. Whole-body scintigraphy demonstrated tumor localization with 131I-labeled fragments without background subtraction. Best tumor contrast, as quantitated by analyzing digital computer scans, was obtained between Days 2 and 5 after injection. Tumor contrast was significantly enhanced when a mixture of both MAb F(ab')2 fragments was used. The biologic half-life of the MAb mixture in the tumor was significantly greater than that of either MAb alone, suggesting the use of the MAb mixture in radioimmunotherapy.

Animals↗
PubMed1986

Enhancement of tumor contrast on radioimmunoscans by using mixtures of monoclonal antibody F(ab')2 fragments.

F(ab')2 fragments of MAbs GA 73-3 (IgG 2 a) and CO 29.11 (IgG 1), which detect distinct antigenic determinants on adenocarcinoma cells of the gastrointestinal tract, were labeled with 131I using the iodogen method. 41 nude mice bearing SW-948 CRC tumors were injected either with a mixture of 100 microCi (11 micrograms) each (n = 9) of the two 131I-F(ab')2 fragments or with either fragment alone at various doses (each group consisting of 8 mice): GA 73-3, 100 microCi (11 micrograms) and 200 microCi (25 micrograms); CO 29.11, 100 microCi (11 micrograms) and 200 microCi (26 micrograms). Whole-body images of the mice were obtained daily for up to six days after injection. Ratios of cpm/pixel in the tumor to those in the rest of the body (rob), representing tumor contrast, were significantly (p less than 0.05) higher in the group of mice injected with the mixture (3.9 +/- 1.5) as compared to those given 100 or 200 microCi of either fragment separately. The biological half-life (T1/2 biol.) of the mixture (44.7 +/- 14.5 h) in the CRC tumors was significantly (p less than 0.05) longer than T1/2 biol. determined in the groups given either fragment alone. T1/2 biol. in the rob was similar in all groups of mice examined.

Animals↗