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Results for “Immunoconjugates”

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At least 235 records · Page 13Linked to original sources
PubMed1993

[A new application of immunoconjugate to reduce the local recurrence of colorectal cancer].

To examine whether or not immunoconjugate-A7-NCS can contribute for the reduction of local recurrence of colorectal cancer, the present study was undertaken. The study included examination of local retension, lymphatic delivery and inhibitory effect on tumor development after local administration of A7-NCS. The result showed that locally injected A7-NCS showed a high local retension, a high regional lymph node accumulation and a high inhibitory effect on tumor development. This finding indicates that A7-NCS can be a new promising tool for reducing the local recurrence of colorectal cancer.

Animals↗
PubMed2004

Synthesis of metal-carbonyl-dendrimer-antibody immunoconjugates: towards a new format for carbonyl metallo immunoassay.

We report the preparation of metal-carbonyl-dendrimer-antibody conjugates. These metal-carbonyl-multilabeled antibodies are designed to be used in a new solid-phase-format carbonyl metallo immunoassay (CMIA). A fourth-generation polyamidoamine dendrimer was labeled with 10-25 (eta5-cyclopentadienyl)iron dicarbonyl (eta1-N-succinimidyl) entities. An antibody was chemically modified at its carbohydrate chains by a site-directed process used to preserve the antigen-antibody binding site. The antibody was then coupled with the dendrimer labeled with 10 metal carbonyl groups. An average of 1.4 labeled dendrimers were grafted per antibody molecule. These metal-carbonyl-dendrimer-antibody conjugates were used as new universal detection reagents that recognize their specific antigens. The antigens were spotted onto nitrocellulose membranes and detected by using the conjugates in combination with Fourier transform infrared spectroscopy. A detection level in the range 5-200 pmol per membrane was achieved. This approach opens the way to a new CMIA format.

Animals↗
PubMed1996

Effectiveness of an adriamycin immunoconjugate that recognizes the C-erbB-2 product on breast cancer cell lines.

Adriamycin (ADM) was chemically conjugated to a murine monoclonal antibody, A0011, which recognizes the c-erbB-2 product, via a disulfide bond using N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolane (2-IT). The molar ratio of ADM to the monoclonal antibody ranged from 15:1 to 25:1 and enzyme-linked immunosorbent assay (ELISA) showed that the binding activity of the conjugate was almost retained. We compared the efficacy of A0011 alone, ADM alone, the A0011-ADM conjugate, against the human breast cancer cell lines SK-BR-3, MDA-MB-361, MCF-7, and BT-20. The A0011-ADM conjugate was observed to be ten times more cytotoxic to the cell lines overexpressing the c-erbB-2 product, namely, SK-BR-3 and MDA-MB-361, than free ADM, but it showed weak cytotoxicity against the cell lines with a low level of c-erbB-2 product expression, namely, MCF-7 and BT-20. However, free A0011 and nonspecific murine IgM-ADM conjugate showed no cytotoxicity toward any of the four cell lines, while the addition of a tenfold molar excess of A0011 inhibited conjugate cytotoxicity. These data suggest that conjugate cytotoxicity is antibody-mediated. Moreover, conjugate cytotoxicity at 10(-6)M was correlated with antigen volume, and the data were fitted to the regression equation y = -11.63logX + 116.38 where the correlation coefficient = 0.950. Our results indicate that targeting therapy aiming at the c-erbB-2 product may be useful in the treatment of breast cancers overexpressing the c-erbB-2 product.

Antibiotics, Antineoplastic↗
PubMed1996

Pretargeted tumour imaging with streptavidin immunoconjugates of monoclonal antibody CC49 and 111In-DTPA-biocytin.

Pretargeted tumour imaging was performed in nude mice bearing subcutaneous LS174T human colon cancer xenografts with streptavidin-CC49 monoclonal antibody and 111In-DTPA-biocytin. Mice were administered 250 micrograms of streptavidin-CC49, followed 6 or 9 days later by 40 ng (250 microCi) of 111In-DTPA-biocytin. Tumors were visualized at 24 h postinjection of 111In-DTPA-biocytin. Tumour uptake was 0.9-2.5% injected dose/g with tumour/nontarget ratios from 2:1 to 37:1 (except for kidney, which was 0.5-3:1). Tumour uptake in mice pretargeted with streptavidin or streptavidin-conjugated nonspecific normal mouse IgG was < 0.1% i.d./g.

Animals↗
PubMed2005

A reversed-phase high-performance liquid chromatography method for analysis of monoclonal antibody-maytansinoid immunoconjugates.

A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for detection and quantification of free maytansinoid drug in disulfide-linked conjugates between monoclonal antibodies and the maytansinoid drug DM1 (MAb-DM1). Mobile phases and gradient conditions were optimized for separation of several DM1-related free drug species from MAb-DM1 conjugates. The selectivity, linearity, and reproducibility of the method are reported. Reduction of the disulfide-linked DM1 followed by RP-HPLC allowed estimation of purity of MAb-linked DM1 as well as recovery of L-DM1. The method was also used to estimate drug per MAb ratios, which were consistent with those determined by UV spectroscopy.

Antibodies, Monoclonal↗
PubMed2006

Monoclonal antibodies and immunoconjugates in acute myeloid leukemia.

The use of monoclonal antibodies for patients with acute myeloid leukemia is based on targeting cell-surface antigens preferentially expressed on leukemic blasts while sparing normal cells and tissues. The majority of studies performed to date have used antibodies reactive with the CD33 antigen. Phase II studies have demonstrated antileukemic responses with all agents, although less so with unlabeled antibodies. The most promising results have been obtained in the treatment of minimal residual disease in patients with acute promyelocytc leukemia. Antibody-targeted chemotherapy with gemtuzumab ozogamicin has also shown significant activity in patients with relapsed acute myeloid leukemia. Radioimmunotherapy with beta-particle emitters may be most effective for the treatment of bulky disease or as part of a conditioning regimen for hematopoietic stem-cell transplantation, whereas radioimmunotherapy with alpha-particle emitters may be better suited to the treatment of small-volume or minimal residual leukemia. Whether or not monoclonal antibody therapy will improve disease outcome compared with conventional treatment regimens remains to be demonstrated by well-designed clinical trials.

Acute Disease↗
PubMed2006

A randomized, multicenter study to determine the safety and efficacy of the immunoconjugate SGN-15 plus docetaxel for the treatment of non-small cell lung carcinoma.

PURPOSE: Chemotherapy prolongs survival and improves quality of life (QOL) for good performance status (PS) patients with advanced non-small cell lung cancer (NSCLC). Targeted therapies may improve chemotherapy effectiveness without worsening toxicity. SGN-15 is an antibody-drug conjugate (ADC), consisting of a chimeric murine monoclonal antibody recognizing the Lewis Y (Le(y)) antigen, conjugated to doxorubicin. Le(y) is an attractive target since it is expressed by most NSCLC. SGN-15 was active against Le(y)-positive tumors in early phase clinical trials and was synergistic with docetaxel in preclinical experiments. This Phase II, open-label study was conducted to confirm the activity of SGN-15 plus docetaxel in previously treated NSCLC patients. EXPERIMENTAL DESIGN: Sixty-two patients with recurrent or metastatic NSCLC expressing Le(y), one or two prior chemotherapy regimens, and PS< or =2 were randomized 2:1 to receive SGN-15 200 mg/m2/week with docetaxel 35 mg/m2/week (Arm A) or docetaxel 35 mg/m2/week alone (Arm B) for 6 of 8 weeks. Intrapatient dose-escalation of SGN-15 to 350 mg/m2 was permitted in the second half of the study. Endpoints were survival, safety, efficacy, and quality of life. RESULTS: Forty patients on Arm A and 19 on Arm B received at least one treatment. Patients on Arms A and B had median survivals of 31.4 and 25.3 weeks, 12-month survivals of 29% and 24%, and 18-month survivals of 18% and 8%, respectively. Toxicity was mild in both arms. QOL analyses favored Arm A. CONCLUSIONS: SGN-15 plus docetaxel is a well-tolerated and active second and third line treatment for NSCLC patients. Ongoing studies are exploring alternate schedules to maximize synergy between these agents.

Adult↗
PubMed2003

Delivery of pharmacologically active dexamethasone into activated endothelial cells by dexamethasone-anti-E-selectin immunoconjugate.

To deliver selectively anti-inflammatory agents into activated endothelial cells, drug-targeting conjugates were developed. Dexamethasone (Dexa) was covalently linked to a monoclonal antibody specifically recognizing E-selectin, which is strongly upregulated in endothelial cells at inflammatory sites. In the present study, the pharmacological effects of this Dexa-mouse antihuman E-selectin antibody (H18/7) (Ab(hEsel)) conjugate were investigated and compared to the effects obtained by free Dexa in human umbilical vein endothelial cells. Flow cytometry and ELISA were performed to analyze the levels of cell adhesion molecules (ICAM-1 and VCAM-1) and secreted cytokines (IL-6 and IL-8). The studies were extended by analysis of a complex gene expression pattern, using a cDNA expression array containing 268 genes encoding human cytokines/cytokine-receptors. Fifty genes and 28 genes were upregulated (ratio> or =2) upon incubation of human umbilical vein endothelial cells with TNFalpha for 6 and 24hr, respectively. This gene expression profile was markedly altered when cells were activated with TNFalpha in the presence of Dexa (100 nM) or Dexa-Ab(hEsel) conjugate (10 micro g/mL conjugate corresponding to 100 nM Dexa). Relative and competitive RT-PCR analysis verified downregulation of TNFalpha-mediated expression of CD40L and IL-8 by Dexa and Dexa-Ab(hEsel), respectively. These results indicated a successful internalization and processing of Dexa-Ab(hEsel) in activated endothelial cells, allowing the intracellularly delivered Dexa to exert its pleiotropic anti-inflammatory activity.

Animals↗
PubMed2002

A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells.

We report a new tumor-directed immunoRNase, a chimeric protein made up of an antibody fragment (single-chain Fv fragment) directed to ErbB2, a cell surface receptor, and a non-toxic, human ribonuclease, which upon cell internalization becomes cytotoxic. The immunoRNase is active as a ribonuclease, specifically binds and selectively kills ErbB2-positive cells. ErbB2 is one of the most specific tumor-associated antigens identified so far, overexpressed on tumor cells of different origin. Its choice as target antigen and that of a non-toxic, human RNase as the killer moiety makes this immunoRNase a new, potentially attractive anticancer agent.

Antigens, Neoplasm↗
PubMed1998

Mimetic ligand-based affinity purification of immune complexes and immunoconjugates.

We developed a simple purification method to purify alkaline phosphatase/anti-alkaline phosphatase IgG as immune complexes using mimetic affinity chromatography wherein the antibody was either a monospecific antibody, a bispecific antibody or a commercial polyclonal IgG conjugated with alkaline phosphatase (AP-IgG) covalently. The immune complexes or conjugates were efficiently bound on the mimetic Blue A6XL column and eluted under mild conditions (5-20 mM phosphate buffer). A similar strategy of purifying peroxidase/anti-peroxidase antibody complexes was also successfully demonstrated using the mimetic Red 3 column. Mimetic affinity chromatography thus appears to be a simple method to purify the desired monospecific or bispecific antibodies from the respective hybridomas and quadromas.

Alkaline Phosphatase↗
PubMedDate not supplied

Characterization of hapten binding to immunoconjugates by electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) has been used to characterize the covalent binding of different haptens to the enzyme glucose 6-phosphate dehydrogenase. The technique allows one to directly observe the relative amounts of each conjugated species present in a mixture, as well as the average hapten number. These measurements are useful for optimizing reaction conditions to yield a more precisely defined product for use in immunoassays. The results obtained show that ESI-MS with a quadrupole analyzer can be successfully used to analyze mixtures of derivatized proteins in the molecular weight range of 50-60 kDa, where the modifying hapten has a molecular weight as low as 130 Da.

Binding Sites↗