Biomedical subjects

D Iliopoulos

Publications and source records attributed to D Iliopoulos.

29 records · Page 2Linked to original sources

PubMed1989

Inhibition of metastases of a human melanoma xenograft by monoclonal antibody to the GD2/GD3 gangliosides.

A human melanoma variant cell line was obtained from a lung metastasis that arose spontaneously after we inoculated melanoma cells sc into a nude mouse. In this model, IgG2a monoclonal antibody (MAb) ME 36.1 defining the GD2/GD3 gangliosides inhibited melanoma growth at the primary site and metastatic spread of the cells, whereas an IgG1 variant of MAb ME 36.1 inhibited lung metastasis formation only. Possible mechanisms of antitumor effects of MAb ME 36.1 are discussed.

Animals↗

PubMed1989

Specific detection of antibodies in cancer patients following immunotherapy with anti-idiotype.

Assays were compared for specificity and sensitivity in detecting in cancer patients' sera antibodies (Ab) raised during the course of immunotherapy with goat anti-idiotypic antibodies (Ab2) bearing the internal image of a colon carcinoma-associated antigen defined by monoclonal antibody (MAb) CO17-1A (Ab1). The human Ab were tested for binding to tumor cells, isolated tumor antigen (Ag), and Ab2, and for the capacity to inhibit binding of Ab2 to Ab1. Chimeric (human/mouse) MAb CO17-1A was used as a positive control in all assays. Of the four different cell binding assays used, the mixed hemadsorption assay (MHA) showed the highest specificity and sensitivity. For detection of Ag-binding human Ab, the enzyme-linked immunosorbent assay (ELISA) with Ag as target and peroxidase (PO)-labeled anti-human IgG antibodies as tracer for detection of human Ab binding to the target, showed higher specificity and sensitivity as compared to radioimmunoassay (RIA). For detection of human Ab binding specifically to Ab2, three different ELISAs and three RIAs were used. Best results were obtained in the ELISA with anti-human IgG antibodies as target and biotinylated Ab2 as tracer for detection of human Ab binding to the target. Of four different inhibition assays used, the ELISA which measures inhibition of binding of biotinylated Ab2 to Ab1 by human Ab or chimeric antibody at 37 degrees C was the most sensitive and specific. These assays have general applicability for the characterization of human Ab responses in Ab2 vaccination approaches to various tumors and pathogens and therefore provide the basis for the establishment of a correlation between Ab responses and clinical outcome of the disease.

Animals↗

PubMed1989

Idiotypic cascades in cancer patients treated with monoclonal antibody CO17-1A.

We have previously shown that gastrointestinal cancer patients treated with monoclonal antibody CO17-1A (Ab1) developed anti-idiotypic antibodies (Ab2) to the Ab1. We now demonstrate that patients produce anti-anti-idiotypic antibodies (Ab3) to their autologous Ab2. Ab3 were demonstrated in culture supernatants of peripheral blood mononuclear cells from five Ab1-treated patients after stimulation of the cells with heterologous Ab2 that functionally mimicked the tumor antigen (Ag) defined by Ab1 and immunologically cross reacted with the patients' Ab2. Ab3 shared idiotopes with Ab1 and were Ab1-like in their binding specificities to tumor cells, Ag, and Ab2. Such antibodies were also elicited by stimulating cells with Ag. However, they were not produced by stimulating posttreatment mononuclear cells with control proteins or by stimulating pretreatment cells with either Ag or Ab2. Our results demonstrate idiotypic cascades in cancer patients treated with monoclonal antibody. Ag-specific Ab3 responses may underlie delayed clinical responses often observed in cancer patients treated with monoclonal antibodies of various specificities.

Adenocarcinoma↗

PubMed1989

Modulation of cancer patients' immune responses by administration of anti-idiotypic antibodies.

Thirty patients with Dukes stage D colon carcinoma who had undergone operative removal of the primary tumor and had growing hepatic metastases each received four intradermal injections of 0.5-4 mg of alum-precipitated goat anti-idiotypic antibodies (anti-Id). The anti-Id had been produced against murine monoclonal antibody (mAb) CO17-1A, which defines a human colon carcinoma associated antigen. All patients elaborated anti-anti-Id that shared idiotopes with mAb CO17-1A, bound to tumor cells and isolated tumor antigen, and competed with the mAb for binding to tumor cells. The clinical response was monitored by ultrasonography, CT, radionuclide scanning, and serum marker assays. Six patients had partial tumor responses; five of these had received additional booster anti-Id injections along with chemotherapy. Seven patients had stabilized tumor; six had received additional anti-Id, with chemotherapy also in four. Conclusions about the clinical role of such immunization await further study, but in demonstrating a specific response to anti-Id, our results support the use of this approach in human immunotherapy against tumors or pathogens.

Antibodies, Anti-Idiotypic↗

PubMed1988

Functional mimicry of tumor-associated antigens by antiidiotypic antibodies.

Antiidiotypic antibodies (Ab2) have been shown to induce specific immunity against murine and human tumors. Studies in murine tumor systems also have shown that Ab2 immunizations can induce protective immunity against a challenge with tumor cells. Antibodies and cytotoxic/regulatory T cells have been implicated as mediators of the antitumor effects induced by Ab2 immunization in mice. In recent clinical trials, cancer patients immunized with Ab2 that functionally mimic a gastrointestinal tumor-associated antigen developed highly specific antitumor immune responses. Thus Ab2 are promising vaccine candidates in immunotherapy approaches to cancer. The choice of Ab2 as well as optimization of immunization procedures with Ab2 are important considerations in future studies.

Animals↗

PubMed1987

Induction of specific immunity to human colon carcinoma by anti-idiotypic antibodies to monoclonal antibody CO17-1A.

Anti-idiotypic antibodies (Ab2) to murine monoclonal antibody (mAb) CO17-1A (Ab1), which defines an antigen associated with human colon carcinoma, were produced in goats. The Ab2 inhibited binding of Ab1 to colon carcinoma cells, and purified tumor antigen inhibited binding of Ab1 to Ab2. The Ab2 elicited in rabbits anti-anti-idiotypic antibodies (Ab3) that bound to cultured human cells of various tissue origins with a binding pattern identical to that of Ab1. Moreover, both Ab1 and Ab3 bound to the isolated tumor antigen, and the Ab3 lysed human colon carcinoma cells in culture in the presence of rabbit complement. Thus, Ab2 raised to mAb CO17-1A are candidates for use in immunotherapy trials in cancer patients.

Animals↗

PubMed1987

Anti-idiotype immunization of cancer patients: modulation of the immune response.

Thirty patients with advanced colorectal carcinoma (CRC) were treated with alum-precipitated polyclonal goat anti-idiotypic antibodies (Ab2) to monoclonal anti-CRC antibody CO17-1A (Ab1) in doses between 0.5 and 4 mg per injection. All patients developed anti-anti-idiotypic antibodies (Ab3) with binding specificities on the surfaces of cultured tumor cells similar to the specificity of Ab1. Furthermore, the Ab3 competed with Ab1 for binding to CRC cells. Fractions of Ab3-containing sera obtained after elution of the serum immunoglobulins from CRC cells bound to purified tumor antigen and inhibited binding of Ab2 to Ab1. The Ab3, therefore, may share idiotopes with Ab1. Six patients showed partial clinical remission and seven patients showed arrest of metastases following immunotherapy. Four of the thirteen patients with measurable clinical responses had received Ab2 alone, whereas 9 patients had also received chemotherapy.

Antibodies, Anti-Idiotypic↗

PubMed1986

Isolation and characterization of a carcinoma-associated antigen.

GA733 is a murine IgG2a monoclonal antibody (MAb) against human gastric carcinoma and is highly tumoricidal in nude mice. The GA733 antigen is a cell surface protein with two subunits of 30,000 and 40,000 daltons. The antigen isolated by immunoaffinity chromatography consists mainly of the 30,000-dalton subunit which bears the GA733 epitope. This subunit displayed several isoelectric points between 6.9 and 7.7. Anti-colon carcinoma MAb 17-1A also detects this antigen, but probably binds to a different epitope.

Antibodies, Monoclonal↗

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↗

PubMedDate not supplied

K-ras oncogene mutations in neoplasias of kidney transplanted patients: preliminary results with a new technique.

K-ras oncogene activations by point mutations are frequent in many forms of human cancers but there is a special category of cancers occurring in immunosuppressed patients after kidney transplantation in which the frequency of K-ras oncogene activation has not been fully studied. We used a new sensitive and easy method for the detection of this mutation, and in 8 DNA samples studied from various neoplasias of 8 patients after kidney transplantation, we found 4 mutations. Our preliminary results indicate that the activation of K-ras oncogene at codon 12, is a common event among the kidney transplanted patients who present a neoplasia, even in the least aggressive forms of the disease, contrary to the sporadic cases.

Adult↗

PubMedDate not supplied

Chromosomal markers associated with metastasis in two colon cancer cell lines established from the same patient.

The purpose of this study was to identify specific chromosomal abnormalities that might be involved in colon cancer metastasis. For this reason, we performed extensive karyotypic analysis on two colon cancer cell lines (SW480 and SW620) established from two surgical biopsies taken at different intervals and representing different stages of the disease from the same patient. Despite the karyotypic heterogeneity, several marker chromosomes were shared between the two cell lines, indicating their common origin. We hypothesized that these shared chromosomal aberrations might be critical for the continuous growth of the tumor cells and, therefore, were retained through progression of the disease. Duplication of 16q and new or additional structural chromosomal abnormalities involving breakpoints 3p21, 8p11, 10q25, 13q14, 14q11 and 15q15 were observed as the characteristic anomalies only in the SW620 cell line. As SW620 was established from the abdominal metastatic lesion of the patient, we postulated that the acquisition of these new markers in the progression steps of the primary tumor might represent "hot-spots" that possibly contain genes crucial for metastatic potential in colon cancer.

Abdominal Muscles↗