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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Sadraeian, Mohammad ; Guimaraes, Francisco E. G. ; Araujo, Ana P. U. ; Worthylake, David K. ; LeCour, Louis Jr. ; Pincus, Seth H.
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 7, AUG 8 2017.
Citações Web of Science: 0

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)

Processo FAPESP: 09/54035-4 - EMU: facility para estudos avançados de materiais nanoestruturados e biossistemas / FAMA
Beneficiário:Igor Polikarpov
Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
Processo FAPESP: 13/07276-1 - CEPOF - Centro de Pesquisa em Óptica e Fotônica
Beneficiário:Vanderlei Salvador Bagnato
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs