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Search results for: Factor VlllC antibody, Monoclonal Antibodies, Host Mouse, Isotype IgG2a

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#31194726   2019/06/13 To Up

Specific activation of pro-Infliximab enhances selectivity and safety of rheumatoid arthritis therapy.

During rheumatoid arthritis (RA) treatment, long-term injection of antitumor necrosis factor α antibodies (anti-TNFα Abs) may induce on-target toxicities, including severe infections (tuberculosis [TB] or septic arthritis) and malignancy. Here, we used an immunoglobulin G1 (IgG1) hinge as an Ab lock to cover the TNFα-binding site of Infliximab by linking it with matrix metalloproteinase (MMP) -2/9 substrate to generate pro-Infliximab that can be specifically activated in the RA region to enhance the selectivity and safety of treatment. The Ab lock significantly inhibits the TNFα binding and reduces the anti-idiotypic (anti-Id) Ab binding to pro-Infliximab by 395-fold, 108-fold compared with Infliximab, respectively, and MMP-2/9 can completely restore the TNFα neutralizing ability of pro-Infliximab to block TNFα downstream signaling. Pro-Infliximab was only selectively activated in the disease site (mouse paws) and presented similar pharmacokinetics (PKs) and bio-distribution to Infliximab. Furthermore, pro-Infliximab not only provided equivalent therapeutic efficacy to Infliximab but also maintained mouse immunity against Listeria infection in the RA mouse model, leading to a significantly higher survival rate (71%) than that of the Infliximab treatment group (0%). The high-selectivity pro-Infliximab maintains host immunity and keeps the original therapeutic efficiency, providing a novel strategy for RA therapy.
Yun-Chi Lu, Chih-Hung Chuang, Kuo-Hsiang Chuang, I-Ju Chen, Bo-Cheng Huang, Wen-Han Lee, Hsin-Ell Wang, Jia-Je Li, Yi-An Cheng, Kai-Wen Cheng, Jaw-Yuan Wang, Yuan-Chin Hsieh, Wen-Wei Lin, Tian-Lu Cheng

1994 related Products with: Specific activation of pro-Infliximab enhances selectivity and safety of rheumatoid arthritis therapy.

5 G1 ml4 Membranes/Box500 MG2 Pieces/Box100μg 6 ml Ready-to-use 1 kit(96 Wells)4 Membranes/Box25 mg4 Arrays/Slide50ug

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#30985291   2019/04/15 To Up

Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice.

Diabetic individuals are at considerable risk for invasive infection by Staphylococcus aureus, however, the mechanisms underlying this enhanced susceptibility to infection are unclear. We observed increased mortality following i.v. S. aureus infection in diabetic mice compared with nondiabetic controls, correlating with increased numbers of low-density neutrophils (LDNs) and neutrophil extracellular traps (NETs). LDNs have been implicated in the inflammatory pathology of diseases such as lupus, given their release of large amounts of NETs. Our goal was to describe what drives LDN increases during S. aureus infection in the diabetic host and mechanisms that promote increased NET production by LDNs. LDN development is dependent on TGF-β, which we found to be more activated in the diabetic host. Neutralization of TGF-β, or the TGF-β-activating integrin αvβ8, reduced LDN numbers and improved survival during S. aureus infection. Targeting S. aureus directly with MEDI4893*, an α toxin-neutralizing monoclonal antibody, blocked TGF-β activation, reduced LDNs and NETs, and significantly improved survival. A comparison of gene and protein expression in high-density neutrophils and LDNs identified increased GPCRs and elevated phosphatase and tensin homolog (PTEN) in the LDN subset. Inhibition of PTEN improved the survival of infected diabetic mice. Our data identify a population of neutrophils in infected diabetic mice that correlated with decreased survival and increased NET production and describe 3 therapeutic targets, a bacterial target and 2 host proteins, that prevented NET production and improved survival.
Taylor S Cohen, Virginia Takahashi, Jessica Bonnell, Andrey Tovchigrechko, Raghothama Chaerkady, Wen Yu, Omari Jones-Nelson, Young Lee, Rajiv Raja, Sonja Hess, C Kendall Stover, John J Worthington, Mark A Travis, Bret R Sellman

1815 related Products with: Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice.

200 1 mg

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#30439343   // To Up

Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice.

Antibody (Ab)-dependent enhancement can exacerbate dengue virus (DENV) infection due to cross-reactive Abs from an initial DENV infection, facilitating replication of a second DENV. Zika virus (ZIKV) emerged in DENV-endemic areas, raising questions about whether existing immunity could affect these related flaviviruses. We show that mice born with circulating maternal Abs against ZIKV develop severe disease upon DENV infection. Compared with pups of naive mothers, those born to ZIKV-immune mice lacking type I interferon receptor in myeloid cells (LysMCreIfnar1) exhibit heightened disease and viremia upon DENV infection. Passive transfer of IgG isolated from mice born to ZIKV-immune mothers resulted in increased viremia in naive recipient mice. Treatment with Abs blocking inflammatory cytokine tumor necrosis factor linked to DENV disease or Abs blocking DENV entry improved survival of DENV-infected mice born to ZIKV-immune mothers. Thus, the maternal Ab response to ZIKV infection or vaccination might predispose to severe dengue disease in infants.
Angela M Fowler, William W Tang, Matthew P Young, Anila Mamidi, Karla M Viramontes, Melanie D McCauley, Aaron F Carlin, Robert T Schooley, Jesica Swanstrom, Ralph S Baric, Jennifer Govero, Michael S Diamond, Sujan Shresta

2426 related Products with: Maternally Acquired Zika Antibodies Enhance Dengue Disease Severity in Mice.

100 μg100 μg100 μg100 μg100 μg100 μg100 μg200 4 Membranes/Box100.00 ug100 μg2 Pieces/Box

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#29859099   2018/06/01 To Up

Proteolytic single hinge cleavage of pertuzumab impairs its Fc effector function and antitumor activity in vitro and in vivo.

Proteolytic impairment of the Fc effector functions of therapeutic monoclonal antibodies (mAbs) can compromise their antitumor efficacy in the tumor microenvironment and may represent an unappreciated mechanism of host immune evasion. Pertuzumab is a human epidermal growth factor receptor 2 (HER2)-targeting antibody and has been widely used in the clinic in combination with trastuzumab for treatment of HER2-overexpressing breast cancer. Pertuzumab susceptibility to proteolytic hinge cleavage and its impact on the drug's efficacy has not been previously studied.
Hao-Ching Hsiao, Xuejun Fan, Robert E Jordan, Ningyan Zhang, Zhiqiang An

1249 related Products with: Proteolytic single hinge cleavage of pertuzumab impairs its Fc effector function and antitumor activity in vitro and in vivo.

96 tests400Tests48 assays48 assays 900 tests96 tests96 assays 1 kit

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#26012567   2015/05/26 To Up

Blocking TWEAK-Fn14 interaction inhibits hematopoietic stem cell transplantation-induced intestinal cell death and reduces GVHD.

Inhibition of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) system reduces intestinal cell death and disease development in several models of colitis. In view of the crucial role of TNF and intestinal cell death in graft-versus-host disease (GVHD) and the ability of TWEAK to enhance TNF-induced cell death, we tested here the therapeutic potential of Fn14 blockade on allogeneic hematopoietic cell transplantation (allo-HCT)-induced intestinal GVHD. An Fn14-specific blocking human immunoglobulin G1 antibody variant with compromised antibody-dependent cellular cytotoxicity (ADCC) activity strongly inhibited the severity of murine allo-HCT-induced GVHD. Treatment of the allo-HCT recipients with this monoclonal antibody reduced cell death of gastrointestinal cells but neither affected organ infiltration by donor T cells nor cytokine production. Fn14 blockade also inhibited intestinal cell death in mice challenged with TNF. This suggests that the protective effect of Fn14 blockade in allo-HCT is based on the protection of intestinal cells from TNF-induced apoptosis and not due to immune suppression. Importantly, Fn14 blockade showed no negative effect on graft-versus-leukemia/lymphoma (GVL) activity. Thus, ADCC-defective Fn14-blocking antibodies are not only possible novel GVL effect-sparing therapeutics for the treatment of GVHD but might also be useful for the treatment of other inflammatory bowel diseases where TNF-induced cell death is of relevance.
Martin Chopra, Andreas Brandl, Daniela Siegmund, Anja Mottok, Viktoria Schäfer, Marlene Biehl, Sabrina Kraus, Carina A Bäuerlein, Miriam Ritz, Katharina Mattenheimer, Stefanie Schwinn, Axel Seher, Thomas Grabinger, Hermann Einsele, Andreas Rosenwald, Thomas Brunner, Andreas Beilhack, Harald Wajant

1691 related Products with: Blocking TWEAK-Fn14 interaction inhibits hematopoietic stem cell transplantation-induced intestinal cell death and reduces GVHD.

100ug Lyophilized100 µg1 x 10^6 cells/vial3 inhibitors96 assays100ug Lyophilized2ug5 Modulators400 ug100ug Lyophilized100ug Lyophilized100 ug

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#25628391   2015/01/27 To Up

Discovery of anti-claudin-1 antibodies as candidate therapeutics against hepatitis C virus.

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Mayo Yamashita, Manami Iida, Minoru Tada, Yoshitaka Shirasago, Masayoshi Fukasawa, Shotaro Nagase, Akihiro Watari, Akiko Ishii-Watabe, Kiyohito Yagi, Masuo Kondoh

1859 related Products with: Discovery of anti-claudin-1 antibodies as candidate therapeutics against hepatitis C virus.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug100ug100ug100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized

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#25091294   2014/08/05 To Up

A new strategy to deliver synthetic protein drugs: self-reproducible biologics using minicircles.

Biologics are the most successful drugs used in anticytokine therapy. However, they remain partially unsuccessful because of the elevated cost of their synthesis and purification. Development of novel biologics has also been hampered by the high cost. Biologics are made of protein components; thus, theoretically, they can be produced in vivo. Here we tried to invent a novel strategy to allow the production of synthetic drugs in vivo by the host itself. The recombinant minicircles encoding etanercept or tocilizumab, which are synthesized currently by pharmaceutical companies, were injected intravenously into animal models. Self-reproduced etanercept and tocilizumab were detected in the serum of mice. Moreover, arthritis subsided in mice that were injected with minicircle vectors carrying biologics. Self-reproducible biologics need neither factory facilities for drug production nor clinical processes, such as frequent drug injection. Although this novel strategy is in its very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics.
Hyoju Yi, Youngkyun Kim, Juryun Kim, Hyerin Jung, Yeri Alice Rim, Seung Min Jung, Sung-Hwan Park, Ji Hyeon Ju

1331 related Products with: A new strategy to deliver synthetic protein drugs: self-reproducible biologics using minicircles.

0.5mg100 5 100ul1 mg10 1mg100 100ug100uL100ug

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#24947844   2014/06/26 To Up

IgG1 anti-epidermal growth factor receptor antibodies induce CD8-dependent antitumor activity.

Anti-EGFR monoclonal antibodies (mAb) like Cetuximab are commonly used for treatment of EGFR+ solid tumors mainly by exerting their therapeutic effect through inhibition of signal transduction. Additionally, IgG1 is a potent mediator of antibody-dependent cytotoxicity (ADCC). In case of the IgG1, Cetuximab induction of ADCC in vivo is controversially discussed. In our study, we investigated the efficiency of Cetuximab-mediated ADCC in a humanized mouse tumor model in vivo and analyzed the contribution of immunologic processes toward antitumor activity. Therefore, we used immunodeficient NOD/Scid mice transgenic for human MHC class I molecule HLA-A2 and adoptively transferred human HLA-A2+ PBMC after engraftment of human epidermoid cell carcinoma A431. Here, we show that high doses of anti-EGFR mAb induced strong tumor regression independent of the immune system. However, tumor regression by low doses of anti-EGFR mAb treatment was ADCC dependent and mediated by tumor infiltrating CD8+ T effector cells. This novel mechanism of ADCC conducted by CD8+ T effector cells was restricted to IgG1 anti-EGFR mAb, dependent of binding to CD16 on T cells and could be inhibited after EGFR blockade on tumor cells. Furthermore, CD8+ T effector cell-mediated ADCC was enhanced in the presence of IL-15 and strongly improved after glycosylation of anti-EGFR mAb indicating the potential of glycoengineered therapeutic mAb as efficient biologicals in cancer therapy.
Jan Kubach, Mario Hubo, Christiane Amendt, Christopher Stroh, Helmut Jonuleit

1141 related Products with: IgG1 anti-epidermal growth factor receptor antibodies induce CD8-dependent antitumor activity.

100.00 ug100 μg100.00 ug100.00 ug2 Pieces/Box100.00 ug100.00 ug0.1ml (1mg/ml)100.00 ug100.00 ug100.00 ug100.00 ug

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#23716675   2013/05/28 To Up

Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens.

Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A β-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.
Colette Cywes-Bentley, David Skurnik, Tanweer Zaidi, Damien Roux, Rosane B Deoliveira, Wendy S Garrett, Xi Lu, Jennifer O'Malley, Kathryn Kinzel, Tauqeer Zaidi, Astrid Rey, Christophe Perrin, Raina N Fichorova, Alexander K K Kayatani, Tomas Maira-Litràn, Marina L Gening, Yury E Tsvetkov, Nikolay E Nifantiev, Lauren O Bakaletz, Stephen I Pelton, Douglas T Golenbock, Gerald B Pier

1595 related Products with: Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens.

200 ug100ug Lyophilized100 TESTS1 ml200 ug25 µg100ug Lyophilized200 ug0.25 mg100ug Lyophilized200 ug0.1 ml

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#19181384   2009/02/01 To Up

Enforced covalent trimerisation of soluble feline CD134 (OX40)-ligand generates a functional antagonist of feline immunodeficiency virus.

The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumour necrosis factor receptor superfamily (TNFRSF) and all primary viral strains tested to date use CD134 for infection. To investigate the effect of the natural ligand for CD134 on FIV infection, feline CD134L was cloned and expressed in soluble forms. However, in contrast to murine or human CD134L, soluble feline CD134L (sCD134L) did not bind to CD134. Receptor-binding activity was restored by enforced covalent trimerisation following the introduction of a synthetic trimerisation domain from tenascin (TNC). Feline and human TNC-CD134Ls retained the species-specificity of the membrane-bound forms of the ligand while murine TNC-CD134L displayed promiscuous binding to feline, human or murine CD134. Feline and murine TNC-CD134Ls were antagonists of FIV infection; however, potency was both strain-specific and substrate-dependent, indicating that the modulatory effects of endogenous sCD134L, or exogenous CD134Lbased therapeutics, may vary depending on the viral strain.
Brian J Willett, Elizabeth L McMonagle, Nicola Logan, Pascal Schneider, Margaret J Hosie

2355 related Products with: Enforced covalent trimerisation of soluble feline CD134 (OX40)-ligand generates a functional antagonist of feline immunodeficiency virus.

100 1 mL250 ug1 mL250 ug1 mL250 ug100 1 mL250 ug100 0.25 mg

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