Gene therapy approaches to HIV-infection: immunological strategies: use of T bodies and universal receptors to redirect cytolytic T-cells.

Abstract

Combined regimens of classical antiviral treatments have not, until now, lead to the eradication of HIV-1. A specific anti-HIV immune response may have to be boosted or transferred to patients after suppression of viral replication, in order to eradicate residual infected cells from their sanctuaries. Cytotoxic T cells engineered to express recombinant chimeric receptors can be redirected against HIV-infected cells and could represent the basis of a new type of immunotherapy. Several HIV epitopes have been targeted successfully in vitro. Two types of binding domains (antibody fragments, CD4) fused with various signal transducing units (zeta chain of the CD3 complex, Fc epsilon RI gamma chain) have been tested for their ability to redirect effector cells to HIV infected lymphocytes. CD4-zeta-expressing myeloid and natural killer cells conferred SCID mice protection against challenge with tumor cells expressing HIV-env. Finally, the safety of the adoptive transfer of syngeneic CD4-zeta -modified T cells in HIV-infected individuals is currently under evaluation.