Elimination of HIV-1 infection by treatment with a doxorubicin-conjugated anti-envelope antibody
2006 (English)In: AIDS (London), ISSN 0269-9370, Vol. 20, no 15, 1911-1915 p.Article in journal (Refereed) Published
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. © 2006 Lippincott Williams & Wilkins.
Place, publisher, year, edition, pages
2006. Vol. 20, no 15, 1911-1915 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-35152DOI: 10.1097/01.aids.0000247111.58961.60Local ID: 25285OAI: oai:DiVA.org:liu-35152DiVA: diva2:256000