About: Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma

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About: Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma
Creator	Sui, Jianhua Han, Thomas Zhu, Quan Chang, De-Kuan Campbell, James Muvaffak, Asli Abdel-Motal, Ussama Kupper, Thomas Marasco, Wayne
source	PMC
abstract	BACKGROUND: Although several therapeutic options have become available for patients with Cutaneous T-cell Lymphoma (CTCL), no therapy has been curative. Recent studies have demonstrated that CTCL cells overexpress the CC chemokine receptor 4 (CCR4). METHODOLOGY/PRINCIPAL FINDINGS: In this study, a xenograft model of CTCL was established and a recombinant adeno-associated viral serotype 8 (AAV8) vector expressing a humanized single-chain variable fragment (scFv)-Fc fusion (scFvFc or “minibody”) of anti-CCR4 monoclonal antibody (mAb) h1567 was evaluated for curative treatment. Human CCR4(+) tumor-bearing mice treated once with intravenous infusion of AAV8 virions encoding the h1567 (AAV8-h1567) minibody showed anti-tumor activity in vivo and increased survival. The AAV8-h1567 minibody notably increased the number of tumor-infiltrating Ly-6G(+) FcγRIIIa(CD16A)(+) murine neutrophils in the tumor xenografts over that of AAV8-control minibody treated mice. Furthermore, in CCR4(+) tumor-bearing mice co-treated with AAV8-h1567 minibody and infused with human peripheral blood mononuclear cells (PBMCs), marked tumor infiltration of human CD16A(+) CD56(+) NK cells was observed. The h1567 minibody also induced in vitro ADCC activity through both mouse neutrophils and human NK cells. CONCLUSIONS/SIGNIFICANCE: Overall, our data demonstrate that the in vivo anti-tumor activity of h1567 minibody is mediated, at least in part, through CD16A(+) immune effector cell ADCC mechanisms. These data further demonstrate the utility of the AAV-minibody gene transfer system in the rapid evaluation of candidate anti-tumor mAbs and the potency of h1567 as a potential novel therapy for CTCL.
has issue date	2012-09-04(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0044455
bibo:pmid	22973452
has license	cc-by
sha1sum (hex)	99e7ae6647b3aef265d79aa84720e5e5b584118d
schema:url	https://doi.org/10.1371/journal.pone.0044455
resource representing a document's title	Human Anti-CCR4 Minibody Gene Transfer for the Treatment of Cutaneous T-Cell Lymphoma
has PubMed Central identifier	PMC3433438
has PubMed identifier	22973452
schema:publication	PLoS One
resource representing a document's body	covid:99e7ae6647b3aef265d79aa84720e5e5b584118d#body_text
is schema:about of	named entity 'CUTANEOUS T-CELL LYMPHOMA' named entity 'studies' named entity 'Gene' named entity 'NO THERAPY' named entity 'PATIENTS' named entity 'CCR4' named entity 'BACKGROUND' named entity 'STUDIES' named entity 'DEMONSTRATED' named entity 'CUTANEOUS T-CELL LYMPHOMA' named entity 'OVEREXPRESS' named entity 'MINIBODY' named entity 'RECENT' named entity 'THERAPEUTIC' named entity 'HAVE' named entity 'TREATMENT' named entity 'CURATIVE' named entity 'CTCL' named entity 'AVAILABLE' named entity 'CC CHEMOKINE RECEPTOR 4' named entity 'CELLS' named entity 'OPTIONS' named entity 'HUMAN' named entity 'GENE TRANSFER' covid:arg/99e7ae6647b3aef265d79aa84720e5e5b584118d named entity 'patients' named entity 'Cutaneous T-Cell Lymphoma' named entity 'CCR4' named entity 'AAV8' named entity 'gene delivery' named entity 'mAb' named entity 'fluorescence-activated cell sorting' named entity 'SCID' named entity 'effector cells' named entity 'Mac-1' named entity 'polyethylenimine' named entity 'CCR4' named entity 'divalent' named entity 'subcutaneously' named entity 'Caliper Life Sciences' named entity 'inoculation' named entity 'Mac-1' named entity 'gene' named entity 'CCR4' named entity 'NK cells' named entity 'AAV' named entity 'GenMab' named entity 'CTCL' named entity 'mAb' named entity 'AAV' named entity 'gene transfer' named entity 'survival time' named entity 'mAb' named entity 'isoflurane' named entity 'gene transfer' named entity 'ADCC' named entity 'CTCL' named entity 'tumor cell' named entity 'CCR10' named entity 'CTCL' named entity 'intravenous' named entity 'tumor growth' named entity 'CCR4' named entity 'cloning vector' named entity 'IgG' named entity 'Tregs' named entity 'leukemic' named entity 'neutrophils' named entity 'CCR4' named entity 'Mac-1' named entity 'cytotoxicity' named entity 'CCR4' named entity 'tumor'

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