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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope

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Author(s):
Sadraeian, Mohammad ; Guimaraes, Francisco E. G. ; Araujo, Ana P. U. ; Worthylake, David K. ; LeCour, Louis Jr. ; Pincus, Seth H.
Total Authors: 6
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 7, AUG 8 2017.
Web of Science Citations: 2
Abstract

Immunotoxins (ITs), which consist of antibodies conjugated to toxins, have been proposed as a treatment for cancer and chronic infections. To develop and improve the ITs, different toxins such as ricin, have been used, aiming for higher efficacy against target cells. The toxin pulchellin, isolated from the Abrus pulchellus plant, has similar structure and function as ricin. Here we have compared two plant toxins, recombinant A chains from ricin (RAC) and pulchellin (PAC) toxins, for their ability to kill HIV Envexpressing cells. In this study, RAC and PAC were produced in E. coli, and chromatographically purified, then chemically conjugated to two different anti-HIV monoclonal antibodies (MAbs), anti-gp120 MAb 924 or anti-gp41 MAb 7B2. These conjugates were characterized biochemically and immunologically. Cell internalization was studied by flow cytometry and confocal microscopy. Results showed that PAC can function within an effective IT. The ITs demonstrated specific binding against native antigens on persistently HIV-infected cells and recombinant antigens on Env-transfected cells. PAC cytotoxicity appears somewhat less than RAC, the standard for comparison. This is the first report that PAC may have utility for the design and construction of therapeutic ITs, highlighting the potential role for specific cell targeting. (AU)

FAPESP's process: 09/54035-4 - Facility for advanced studies of biosystems and nanostructured materials
Grantee:Igor Polikarpov
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 13/07276-1 - CEPOF - Optics and Photonic Research Center
Grantee:Vanderlei Salvador Bagnato
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC