SINGLE CHAIN ANTIGEN RECOGNIZING CONSTRUCTS (scARCs) STABILIZED BY THE INTRODUCTION OF NOVEL DISULFIDE BONDS

摘要

The present invention relates to a single chain antigen recognizing construct (scARC), which is composed of stabilized variable domains by the introduction of novel disulfide bonds, in order to prevent residual mis-pairing with endogenous ARC chains. The invention further discloses a method for the design of a novel structurally stabilized scARC, the method being based on the visual inspection of the crystal structure of the underlying scARC and the selection of appropriate amino acid substitutions to generate a novel disulfide bond in the protein structure. Furthermore, the invention discloses a method for the production of a cell which expresses the scARC of the invention. Also described are nucleic acids encoding an inventive scARC, as well as DNA and RNA constructs that allow for the expression of the inventive scARC. The invention further encompasses pharmaceutical compositions containing the scARC of the invention and the use of the scARC in therapy of cancerous or infectious diseases, or for use in the quantification and/or visualization of disease associated antigens.