TARGETING OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CELLS BY CD8(-LYMPHOCYTES ARMED WITH UNIVERSAL T-CELL RECEPTORS() T)

We have developed an immunotherapeutic approach with potential applica tion in the treatment of viral and malignant disease. We show that pri mary CD8(+) T cells isolated from peripheral blood can be genetically modified by retroviral transduction to express high levels of universa l (major histocompatibility complex-unrestricted) chimeric T-cell rece ptors specific for human immunodeficiency virus (HIV) antigens. Two cl asses of HIV-specific URs in which the antigen-binding domain is compr ised of either CD4 or a single-chain antibody are capable of activatin g a number of T-cell effector functions in response to target cells, i ncluding cytolysis, in a highly sensitive and specific manner. Importa ntly, we have addressed a number of issues which, although particularl y relevant to the clinical application of this approach in the treatme nt of HIV infection, may also impact on the potential of UR immunother apy for other disease targets. The UR immunotherapeutic system is part icularly suited for evaluation in the clinical setting. (C) 1994 by Th e American Society of Hematology.