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Find video protocols related to scientific articles indexed in Pubmed.
Asymmetrical Fc engineering greatly enhances ADCC effector function and stability of the modified antibodies.
J. Biol. Chem.
PUBLISHED: 12-05-2013
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Antibody Dependent Cellular Cytotoxicity (ADCC) is mediated through the engagement of Fc segment of antibodies with Fc gamma receptors (Fc?Rs) on immune cells upon binding of tumor or viral antigen. Co-crystal structure of Fc?RIII in complex with Fc revealed that Fc binds to Fc?RIII asymmetrically with two Fc chains contacting separate regions of the Fc?RIII by utilizing different residues. To fully explore this asymmetrical nature of Fc:Fc?R interaction, we screened more than 9,000 individual clones in Fc heterodimer format in which different mutations were introduced at the same position of two Fc chains using a high throughput competition AlphaLISA assay. To this end, we have identified a panel of novel Fc variants with significant binding improvement to Fc?RIIIA (both F158 and V158 allotypes), increased ADCC activity in vitro and strong tumor growth inhibition in mice xenograft human tumor models. Compared to previously identified Fc variants in conventional IgG format, Fc heterodimers with asymmetrical mutations can achieve similar or superior potency in ADCC-mediated tumor cell killing and demonstrate improved stability in CH2 domain. Fc heterodimers also allow more selectivity toward activating Fc?RIIA than inhibitory Fc?RIIB. Afucosylation of Fc variants further increases the affinity of Fc to Fc?RIIIA, leading to much higher ADCC activity. The discovery of these Fc variants will potentially open up new opportunities in building the next generation of therapeutic antibodies with enhanced ADCC effector function for the treatment of cancers and infectious diseases.
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Herpesvirus saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor.
J. Immunol.
PUBLISHED: 10-21-2011
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Herpesvirus Saimiri gene 13 (HVS13) exhibits 57% identity with the predicted sequence of a T cell-derived molecule termed CTLA8. Recombinant HVS13 and CTLA8 stimulate transcriptional factor NF-kappaB activity and Interleukin-6 (IL-6) secretion in fibroblasts, and costimulate T cell proliferation. An HVS13.Fc fusion protein was used to isolate a cDNA encoding a novel receptor that also binds CTLA8. This receptor is unrelated to previously identified cytokine receptor families. A recombinant soluble receptor inhibited T cell proliferation and IL-2 production induced by PHA, concanavalin A (conA), and anti-TCR MAb. These results define CTLA8 and HVS13 as novel cytokines that bind to a novel cytokine receptor. We propose to call these molecules IL-17, vIL-17, and IL-17R, respectively.
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Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand.
Blood
PUBLISHED: 08-12-2011
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X-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.03 mg/kg for 22 weeks, and after a 12-week drug-free interval, the dose was increased to 0.05 mg/kg for an additional 22 weeks of treatment. Although specific antibody responses to T cell-dependent antigens was lacking, administration of rCD40 resulted in acquisition of the capacity to mount cutaneous delayed type hypersensitivity reactions that disappeared during the drug-free interval as well as the postbiologic follow-up period. With rCD40L treatment, patient T cells developed a new capacity to respond to T-cell mitogens with synthesis of IFN-? and TNF-?. Intracellular cytokine staining studies showed that both CD4(+) and CD8(+) T cells participated in this response. Finally, CD40L therapy was associated with changes in lymph node size and architecture based on comparison of biopsies taken before and after therapy. This clinical study showed that rCD40L is capable of improving T cell-immune function in patients with XHM.
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Inhibition of angiopoietin-2 in LuCaP 23.1 prostate cancer tumors decreases tumor growth and viability.
Prostate
PUBLISHED: 06-29-2010
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Angiopoietin-2 is expressed in prostate cancer (PCa) bone, liver, and lymph node metastases, whereas, its competitor angiopoietin-1 has limited expression in these tissues. Therefore, we hypothesized that the inhibition of angiopoietin-2 activity in PCa will impede angiogenesis, tumor growth, and alter bone response in vivo.
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AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, inhibits angiogenesis in models of ocular neovascular diseases.
Invest. Ophthalmol. Vis. Sci.
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To determine whether systemic treatment with AMG 386, a selective angiopoietin 1/2-neutralizing peptibody, inhibits neovascular processes in animal models of ocular disease.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.