OBJECTIVE: To test the efficacy of an immunoconjugate against HIV-1. DESIGN: : A murine monoclonal antibody against the envelope antigen of HIV (P4/D10) was conjugated with the conventional anticancer drug, doxorubicin, and tested against infectious virus and infected cells, both in vitro and in vivo. METHODS: P4/D10 antibody was incubated with free virus (neutralization) or HIV-infected cells (inhibition) and the resulting infection was measured by a p24 capture enzyme-linked immunosorbent assay. In an HIV-1/MuLV murine challenge model, the ability of the conjugate to inhibit infection in vivo was measured. RESULTS: Doxorubicin-conjugated P4/D10 neutralized HIV-1IIIB and eliminated intercellular spread and HIV replication in infected Jurkat cells in vitro. The conjugate also protected mice from challenge with HIV-1IIIB/MuLV at an eightfold lower concentration than needed for free antibody, whereas no effects were observed for comparable doses of free drug or irrelevant conjugate controls. CONCLUSION: This indicates that doxorubicin is concentrated to HIV-infected cells by the P4/D10 antibody, significantly (P = 0.0001) contributing to HIV elimination. This concept could also be adapted to eradicate remaining antigen-expressing T cells in patients treated with antiretroviral therapy.
OBJECTIVE: To test the efficacy of an immunoconjugate against HIV-1. DESIGN: : A murine monoclonal antibody against the envelope antigen of HIV (P4/D10) was conjugated with the conventional anticancer drug, doxorubicin, and tested against infectious virus and infected cells, both in vitro and in vivo. METHODS: P4/D10 antibody was incubated with free virus (neutralization) or HIV-infected cells (inhibition) and the resulting infection was measured by a p24 capture enzyme-linked immunosorbent assay. In an HIV-1/MuLV murine challenge model, the ability of the conjugate to inhibit infection in vivo was measured. RESULTS:Doxorubicin-conjugated P4/D10 neutralized HIV-1IIIB and eliminated intercellular spread and HIV replication in infected Jurkat cells in vitro. The conjugate also protected mice from challenge with HIV-1IIIB/MuLV at an eightfold lower concentration than needed for free antibody, whereas no effects were observed for comparable doses of free drug or irrelevant conjugate controls. CONCLUSION: This indicates that doxorubicin is concentrated to HIV-infected cells by the P4/D10 antibody, significantly (P = 0.0001) contributing to HIV elimination. This concept could also be adapted to eradicate remaining antigen-expressing T cells in patients treated with antiretroviral therapy.
Authors: Suzanne J F Kaptein; Tine De Burghgraeve; Mathy Froeyen; Boris Pastorino; Marijke M F Alen; Juan A Mondotte; Piet Herdewijn; Michael Jacobs; Xavier de Lamballerie; Dominique Schols; Andrea V Gamarnik; Ferenc Sztaricskai; Johan Neyts Journal: Antimicrob Agents Chemother Date: 2010-09-13 Impact factor: 5.191
Authors: Chien-Hsing Chang; Jorma Hinkula; Meiyu Loo; Tina Falkeborn; Rongxiu Li; Thomas M Cardillo; Edmund A Rossi; David M Goldenberg; Britta Wahren Journal: PLoS One Date: 2012-07-23 Impact factor: 3.240
Authors: Jing Wen; Ming Yan; Yang Liu; Jie Li; Yiming Xie; Yunfeng Lu; Masakazu Kamata; Irvin S Y Chen Journal: PLoS One Date: 2016-04-06 Impact factor: 3.240