Anthrax toxin is a critical virulence factor of Bacillus anthracis. The toxin comprises protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF), forming bipartite lethal toxin (LT) and edema toxin (ET). PA binds cellular surface receptors and is required for intracellular translocation of the enzymatic moieties. For this reason, anti-PA antibodies have been developed as therapeutics for prophylaxis and treatment of human anthrax infection. Assays described publicly for the control of anti-PA antibody potency quantify inhibition of LT-mediated cell death or the ET-induced increase in c-AMP levels. These assays do not fully reflect and/or capture the pathological functions of anthrax toxin in humans. Herein, we report the development of a cell-based gene reporter potency assay for anti-PA antibodies based on the rapid LT-induced degradation of c-Jun protein, a pathogenic effect that occurs in human cells. This new assay was developed by transducing Hepa1c1c7 cells with an AP-1 reporter lentiviral construct and has been qualified for specificity, accuracy, repeatability, intermediate precision, and linearity. This assay not only serves as a bioassay for LT activity, but has applications for characterization and quality control of anti-PA therapeutic antibodies or other products that target the AP-1 signaling pathway.

01 Jan 2010·Biologie Aujourd'hui

Intérêt des anticorps recombinants dans la protection médicale contre les agents du bioterrorisme : l'exemple de la maladie du charbon

Review

Author: Pelat, Thibault ; Vidal, Dominique ; Thullier, Philippe ; Paucod, Jean-Charles

Recombinant antibodies are a highly successful class of therapeutic molecules, they are well adapted for use against bio-weapons (BW) as they act immediately, are often synergistic with other therapeutic molecules, have a long half-life and are well tolerated. Anthrax is regarded at high risk of being used as BW, and its pathogenic properties depend on toxins, which might be neutralized by antibodies. These toxins are made of three different types of sub-units (PA, LF, EF). Several anti-PA have been developed, including an original approach by our team. We have developed an anti-LF, as recommended by experts. Our anti-PA antibody, and to a lesser extend our anti-LF antibody, will be presented here.

01 Jan 2003·Clinical & Experimental MetastasisQ3 · MEDICINE

Effects of alpha-difluoromethylornithine on local recurrence and pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice.

Q3 · MEDICINE

Article

Author: John F. Harms ; Danny R. Welch ; Laura Craig ; Sharlene Washington ; Lindsay J. Texter ; Andrea Manni ; Laurence M. Demers ; James W. Griffith ; Michael F. Verderame ; Michael Cloud ; David Mauger

We have recently shown that administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine (PA) biosynthesis reduces pulmonary metastasis from MDA-MB-435 breast cancer xenografts in nude mice. The present experiments were designed to further explore PA involvement in breast cancer metastasis, using GFP-tagged MDA-MB-435 cells that can be tracked at the single cell level. Administration of DFMO significantly reduced the number of mice with pulmonary metastasis as well as the number of metastases per mouse. Both single-cell and multicellular metastatic deposits were similarly suppressed, thus suggesting that DFMO was inhibiting lung colonization by tumor cells rather than preventing progression of single-cell deposits to overt metastasis. DFMO administration also significantly reduced local recurrences following removal of the primary tumor. Prolongation of DFMO treatment to 14 weeks did not yield a superior antimetastatic effect beyond that provided by a 10-week course of therapy. Discontinuation of DFMO, on the other hand, was associated with local regrowth of the tumors and, possibly, recurrence of pulmonary metastasis. These data provide a rationale for testing the efficacy of anti-PA treatment within the context of adjuvant therapy of breast cancer.

100 Deals associated with Anthraxumab

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Indication	Highest Phase	Country/Location	Organization	Date
Anthrax	Phase 1	Netherlands	IQ Therapeutics BV	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISC2022	Not Applicable	Ischemic stroke	-	Blank-NPA	ceuhgdnhwg(czbksuzjux) = zpwwiiqfnl mgoaqdczlp (jhukpzuumq ) View more	-	01 Feb 2022
				NG-NPA	ceuhgdnhwg(czbksuzjux) = yqzfdscawo mgoaqdczlp (jhukpzuumq ) View more
ASCO_GI2019	Not Applicable	Hepatocellular Carcinoma	-	DAA therapy	(lclivqpgqp) = vqsyjgfgfq rrlhhhzoub (wqkdozkqjy, 39.5 - not reached) View more	Positive	29 Jan 2019
				No DAA therapy	(lclivqpgqp) = qsytlqovzc rrlhhhzoub (wqkdozkqjy, 9.8 - 14.5)

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