Bispecific single chain molecules (Janusins) target cytotoxic lymphocytes on HIV infected cells.
The human immunodeficiency virus type 1 (HIV-1) uses cell surface CD4 as a receptor to infect susceptible cells. Therefore, different forms of soluble CD4 (sCD4) molecules have been developed recently for potential therapeutic purposes. Here we describe a novel design of sCD4 molecules which exploit cytotoxic T cells as their effector function. The principle of bispecific antibodies was exploited and further developed to create new bispecific reagents which could retarget cytotoxic T cells of any specificity and thus, induce killing of HIV-1 infected cells. The most advanced molecules, Janusins, contain in one polypeptide chain the first two N-terminal CD4 domains and single chain combining site against the human CD3 complex (FvCD3).
Traunecker
A
A
Basel Institute for Immunology, Switzerland.
Lanzavecchia
A
A
Karjalainen
K
K
D000595:Amino Acid Sequence; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001483:Base Sequence; D017252:CD3 Complex; D015704:CD4 Antigens / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005822:Genetic Vectors; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D009841:Oligonucleotides; D011948:Receptors, Antigen, T-Cell