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

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, i...

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Autores principales:	Mohammad Sadraeian, Francisco E. G. Guimarães, Ana P. U. Araújo, David K. Worthylake, Louis Jr. LeCour, Seth H. Pincus
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c255a1dc2eb4c78b4fafd46e461bdcf
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spelling	oai:doaj.org-article:0c255a1dc2eb4c78b4fafd46e461bdcf2021-12-02T15:06:16ZSelective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope10.1038/s41598-017-08037-32045-2322https://doaj.org/article/0c255a1dc2eb4c78b4fafd46e461bdcf2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08037-3https://doaj.org/toc/2045-2322Abstract 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 Env-expressing 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.Mohammad SadraeianFrancisco E. G. GuimarãesAna P. U. AraújoDavid K. WorthylakeLouis Jr. LeCourSeth H. PincusNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohammad Sadraeian Francisco E. G. Guimarães Ana P. U. Araújo David K. Worthylake Louis Jr. LeCour Seth H. Pincus Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope
description	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 Env-expressing 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.
format	article
author	Mohammad Sadraeian Francisco E. G. Guimarães Ana P. U. Araújo David K. Worthylake Louis Jr. LeCour Seth H. Pincus
author_facet	Mohammad Sadraeian Francisco E. G. Guimarães Ana P. U. Araújo David K. Worthylake Louis Jr. LeCour Seth H. Pincus
author_sort	Mohammad Sadraeian
title	Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope
title_short	Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope
title_full	Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope
title_fullStr	Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope
title_full_unstemmed	Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope
title_sort	selective cytotoxicity of a novel immunotoxin based on pulchellin a chain for cells expressing hiv envelope
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0c255a1dc2eb4c78b4fafd46e461bdcf
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Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelope

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