Elimination of HIV-1 infection by treatment with a doxorubicin-conjugated anti-envelope antibody

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-1(IIIB) and eliminated intercellular spread and HIV replication in infected Jurkat cells in vitro. The conjugate also protected mice from challenge with HIV-1(IIIB)/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. (c) 2006 Lippincott Williams & Wilkins.