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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-08037-3 |
| _version_ | 1819127235679879168 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T08:08:42Z |
| format | Article |
| id | doaj.art-0c255a1dc2eb4c78b4fafd46e461bdcf |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-22T08:08:42Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0c255a1dc2eb4c78b4fafd46e461bdcf2022-12-21T18:33:04ZengNature PortfolioScientific Reports2045-23222017-08-017111210.1038/s41598-017-08037-3Selective cytotoxicity of a novel immunotoxin based on pulchellin A chain for cells expressing HIV envelopeMohammad Sadraeian0Francisco E. G. Guimarães1Ana P. U. Araújo2David K. Worthylake3Louis Jr. LeCour4Seth H. Pincus5Instituto de Física de São Carlos, Universidade de São PauloInstituto de Física de São Carlos, Universidade de São PauloInstituto de Física de São Carlos, Universidade de São PauloDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences CenterDepartment of Biochemistry and Molecular Biology, Louisiana State University Health Sciences CenterResearch Institute for Children, Children’s HospitalAbstract 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.https://doi.org/10.1038/s41598-017-08037-3 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-08037-3 |
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