Abstract：
:Conjugates of monoclonal antibodies and Pseudomonas exotoxin A (PE) were formed with disulfide or thioether bonds. Thioether conjugates which formed with succinimidyl 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (SMCC) modified PE and reduced antibody formed with an 80% yield of equimolar conjugate within 30 min with an offering of one to one (toxin:antibody). The efficiency and kinetics of thioether formation were much higher with SMCC than with other maleimide reagents as well as more efficient than disulfide linkers. Thioether linkage resulted in immunotoxin consistently more potent and more selective in vitro than disulfide bonded conjugate. Thioether bonded conjugates also proved to have other favorable in vivo properties compared to disulfide conjugates: (1) a longer half-life in serum; (2) increased tumor localization; and (3) reduced toxicity. Toxicity of thioether linked holotoxin conjugates was directed at the liver hepatocyte but was easily monitored by serum liver enzymes. The conjugates are currently undergoing clinical evaluation for treatment of ovarian cancer with intraperitoneal administration. Research is ongoing to further decrease residual toxicity without reducing the potency of the conjugate.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Morgan AC Jr,Sivam G,Beaumier P,McIntyre R,Bjorn M,Abrams PGdoi
10.1016/0161-5890(90)90140-usubject
Has Abstractpub_date
1990-03-01 00:00:00pages
273-82issue
3eissn
0161-5890issn
1872-9142journal_volume
27pub_type
杂志文章abstract：:Peripheral blood B lymphocytes have been isolated from healthy individuals who were immunized with lymphocytes from HLA-incompatible donors and transformed with Epstein-Barr virus to produce human monoclonal cell lines specific for human HLA molecules. The cell lines have been previously characterized and are known to...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(95)00071-2
更新日期：1995-10-01 00:00:00
abstract：:Rheumatoid arthritis (RA) is a destructive polyarthritis in which synovial-like fibroblasts (SFs) invade and erode cartilage by expressing membrane-anchored type 1 matrix metalloproteinase (MT1-MMP). The mitogen activated protein kinase (MAPK) pathway is activated in RA SFs, but the mechanism of activation is unknown....
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2013.02.001
更新日期：2013-10-01 00:00:00
abstract：:The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins. As KSRP is expressed in immune cells including T and B cells, neutrophils, macrophages and dendritic cells, we wanted...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2017.05.003
更新日期：2017-07-01 00:00:00
abstract：:Concanavalin A (Con A)section-binding proteins from mouse spleen leukocytes were characterised by two-dimensional electrophoresis of material precipitated, by Con A plus anti-Con A, from lysates of biosynthetically-labelled cells. Although most cell surface (iodinatable) proteins are known to bind Con A, some of the m...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(83)90030-5
更新日期：1983-04-01 00:00:00
abstract：:The translation of mRNA within total RNA of German (Blattella germanica) cockroaches was performed using a rabbit reticulocyte lysate system. Analysis of the translation products by SDS-PAGE and combined autoradiography revealed several synthesized proteins with apparent molecular weights ranging from 20 kD to 110 kD....
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(93)90443-f
更新日期：1993-12-01 00:00:00
abstract：:Comparative interactions of purified rabbit C1q with 18-2-3, a high affinity (2-3 X 10(10) M-1) anti-fluorescein (anti-F1) murine monoclonal IgM antibody (pentamer) and constitutive monomeric subunits (IgMs) were studied. Using a solid phase radioimmunoassay (SPRIA), based on immobilized polyvalent antigen, it was sho...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(88)90076-4
更新日期：1988-06-01 00:00:00
abstract：:A variety of important cellular functions are regulated by cytokines. The Jak-STAT pathway is one of the important signaling pathways downstream of cytokine receptors. Following binding of a ligand to its cognate receptor, receptor-associated Jaks are activated. STAT proteins are then in turn activated by tyrosine pho...
journal_title：Molecular immunology
pub_type： 杂志文章,评审
doi：10.1016/s0161-5890(00)00018-3
更新日期：2000-01-01 00:00:00
abstract：:Induction of the TCR signaling pathway terminates the expression of RAG genes, and a link between this pathway and their transcriptional control is evident from the recent demonstration of their re-expression if the TCR is subsequently lost or down-regulated. Since unstimulated T cells display a steady-state level of ...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2011.02.015
更新日期：2011-07-01 00:00:00
abstract：:Human cell lines and blood lymphocytes were treated for short time periods with IFN-gamma. This treatment increased the amount of the assembled MHC class I molecules on the plasma membrane after 30 min. This early increase of the membrane expression subsided in the next few hours. A second wave of elevation occurred a...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(93)90008-y
更新日期：1993-06-01 00:00:00
abstract：:This report demonstrates that a marker of human embryonic endoderm and embryonal carcinoma cells recognized by a hybridoma antibody FC 10.2, involves Type 1 blood group chains with the sequence Gal beta 1 leads to 3G1cNAc beta 1 leads to 3Gal beta 1 leads to 4G1c. This conclusion has been reached from antigenic analys...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(83)90005-6
更新日期：1983-06-01 00:00:00
abstract：BACKGROUND:Bladder cancer (BC) can be successfully treated by manipulating immune responses with intravesical Bacillus Calmette-Guerin instillation or targeting the PD-1/PD-L signaling pathway. In the present study we investigated the prognostic significance of the immune checkpoint inhibitor PD-1 and its ligands PD-L1...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2020.05.010
更新日期：2020-08-01 00:00:00
abstract：:Innate lymphoid cells (ILCs) contribute to the regulation of gastrointestinal (GI) homeostasis. Over the past 15 years, there has been a large effort to dissect the mechanisms required for GI homeostasis, with a major focus on different immune cell populations and the cytokines that they produce. In contrast to T-help...
journal_title：Molecular immunology
pub_type： 杂志文章,评审
doi：10.1016/j.molimm.2017.11.013
更新日期：2019-06-01 00:00:00
abstract：:Toll-like receptors (TLRs) are a family of highly conserved germline-encoded pattern-recognition receptors (PRRs) and are essential for host immune response. Little is known regarding the activation mechanism of TLRs especially of the TLR7/8/9 subfamily. Here we cloned and characterized bovine TLR8 (bTLR8) and found t...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2008.09.024
更新日期：2009-02-01 00:00:00
abstract：:The ragweed allergens Amb t 5 and Amb a 5 are among the smallest inhaled protein allergens known, containing a single, immunodominant T-cell epitope. In this study we analyzed the B-cell epitope structure of Amb t 5. The three-dimensional structures of Amb t 5 and Amb a 5 have been determined by NMR spectroscopy, prov...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/s0161-5890(99)00054-1
更新日期：1998-06-01 00:00:00
abstract：:Cimetidine, a histamine type-2 receptor antagonist, is known to inhibit the growth of several tumors in human and animals, however the mechanism of action underlying this effect remains largely unknown. Here, in the mice model of 3LL lung tumor, cimetidine showed significant inhibition of tumor growth. However, an in ...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2012.10.035
更新日期：2013-05-01 00:00:00
abstract：:The transcription factor NF-kappaB plays critical roles in immune and inflammatory responses. Here we show that filarial parasitic sheath proteins cause activation of NF-kappaB in the airway epithelial HEp-2 cell line. This activation was transient and saturable, and involved degradation of the cytoplasmic inhibitor p...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/s0161-5890(00)00039-0
更新日期：2000-02-01 00:00:00
abstract：:Earlier studies, which provided indirect evidence for the involvement of the C gamma 2 domain of human immunoglobulin G (IgG) in human immunoglobulin G (IgG) in human monocyte binding, have been extended to further localise the site of interaction on human IgG. A number of IgGs from several different species and fragm...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(86)90059-3
更新日期：1986-03-01 00:00:00
abstract：:We previously demonstrated that some fish have unique response in the form of reactive oxygen species (ROS) production. In the present study, we cloned and sequenced the full-length cDNAs for carp (Cyprinus carpio) phagocyte NADPH oxidase components: gp91phox, p22phox, p47phox, p67phox and p40phox. These amino acid se...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2007.09.028
更新日期：2008-03-01 00:00:00
abstract：:The porcine complement proteins C3 and C4 have been isolated and then characterized using small-angle scattering methods. Within the limits of experimental errors, the porcine proteins are virtually identical with the corresponding human proteins as measured in terms of mol. wt, Mr and radius of gyration, R,: Mr(C3) =...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(91)90181-i
更新日期：1991-09-01 00:00:00
abstract：:Mice deficient for SPI-group ETS transcription factors PU.1 or SPI-B fail to generate lymphocytes or do not mount normal antibody mediated immune responses, respectively. PU.1 expression is restricted to B-, T-lymphocytes and macrophages, while SPI-B is expressed in B- and T-lymphocytes. SPI-C is an ETS transcription ...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/s0161-5890(03)00032-4
更新日期：2003-06-01 00:00:00
abstract：:Some IgM cattle antibodies are amongst the largest known to exist in jawed vertebrates where CDR3H size may extend up to 61 amino acids. To understand the origin of such an exceptionally long CDR3H, bovine D(H) gene locus was completely characterized from Holstein cattle that revealed the presence of a total of eight ...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2010.02.014
更新日期：2010-07-01 00:00:00
abstract：:Renal transplantation is the treatment of choice for patients with end-stage renal disease. The vital role of the complement system in renal transplantation is widely recognized. This review discusses the role of complement in the different phases of renal transplantation: in the donor, during preservation, in reperfu...
journal_title：Molecular immunology
pub_type： 杂志文章,评审
doi：10.1016/j.molimm.2017.05.014
更新日期：2017-09-01 00:00:00
abstract：:Dendritic cells (DCs) are the professional antigen-presenting cells (APC) which efficiently prime the immune response or induce tolerance. We recently identified Dendritic Cell Specific TrAnsMembrane Protein (DC-STAMP), a novel 470 amino acid protein preferentially expressed by dendritic cells. Previously we demonstra...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2010.04.019
更新日期：2010-07-01 00:00:00
abstract：:The Fc region of IgG antibodies is crucial for binding to Fc receptors expressed on the surfaces of various immune leukocytes and eliciting therapeutic effector functions such as clearance of antibody-opsonized tumor cells. Despite abrogated Fc gamma receptor (FcγR) binding and therapeutic effector function in the abs...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2019.07.007
更新日期：2019-10-01 00:00:00
abstract：:Multilamellar lipid vesicles (MLV) composed of egg yolk lecithin (EYL) suppressed the response of bovine peripheral blood lymphocytes (BPBL) to phytohemagglutinin (PHA). EYL contains 18:1 and 18:2 as the major unsaturated phospholipids. Dioleoyllecithin (DOL; cis 9) MLV did not suppress BPBL blastogenesis. Dilinoeylle...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(82)90195-x
更新日期：1982-11-01 00:00:00
abstract：:Cell-cell signaling represents an essential hallmark of multicellular organisms, which necessarily require a means of communicating between different cell populations, particularly immune cells. Cytokine receptor signaling through the Janus kinase/Signal Transducer and Activator of Transcription/Suppressor of Cytokine...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2016.02.002
更新日期：2016-03-01 00:00:00
abstract：:Kappa light chains were investigated in sera of several groups of wild derived mouse strains by radioimmunological analysis using xenogeneic anti-mouse kappa light chain antibodies. Although the majority of strains tested expressed serologically indistinguishable kappa chains, several significant exceptions were obser...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(86)90068-4
更新日期：1986-08-01 00:00:00
abstract：:Pulmonary surfactant proteins, SP-A and SP-D, are carbohydrate pattern recognition molecules of innate immunity, which significantly enhance phagocytosis and killing of Aspergillus fumigatus, a pathogenic fungus, by neutrophils and macrophages. The present study examined the susceptibility of immunosuppressed SP-A gen...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2010.02.027
更新日期：2010-06-01 00:00:00
abstract：:The T-cell surface proteins CD4 (L3T4) and CD8 (Lyt2) are first expressed on thymocytes as they undergo maturation in the thymus. Two immature T-lymphoma cell clones SL12.4 and RS4.2 which constitutively express low or undetectable levels of CD4 and CD8 were used to investigate the activation of CD4 and CD8 gene expre...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(91)90087-z
更新日期：1991-01-01 00:00:00
abstract：:Following measles virus (MV) infection, viral peptides are presented to CTL by MHC class I molecules on infected antigen presenting cells at widely different epitope densities. Whereas three MV epitopes (MV-M(211-219), MV-F(438-446) and MV-H(30-38)) derived from different structural proteins occur at regular densities...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/s0161-5890(02)00204-3
更新日期：2003-01-01 00:00:00
