Author/Editor		Golob Urbanc, Anja; Rajčević, Uroš; Strmšek, Žiga; Jerala, Roman
Title		Design of split superantigen fusion proteins for cancer immunotherapy
Type		članek
Vol. and No.		Letnik 294, št. 16
Publication year		2019
Volume		str. 6294-6305
ISSN		0021-9258 - The Journal of biological chemistry
Language		eng
Abstract		Several antibody-targeting cancer immunotherapies have been developed based on T cell activation at the target cells. One of the most potent activators of T cells are bacterial superantigens, which bind to MHC class II on antigen presenting cells and activate T cells through T cell receptor. Strong T cell activation is also one of the main weaknesses of this strategy as it may lead to systemic T cell activation. To overcome the limitation of conventional antibody-superantigen fusion proteins, we have split a superantigen into two fragments, individually inactive, until both fragments came into close proximity and reassemble into a biologically active form capable of activating T cell response. A screening method based on fusion between SEA and coiled-coil heterodimers was developed that enabled detection of functional split SEA designs. The split SEA design that demonstrated efficacy in fusion with coiled-coil dimer forming polypeptides, was fused to a single chain antibody specific for tumor antigen CD20. This design selectively activated T cells by split SEA-scFv fusion binding to target cells.
Keywords		T cell activation cancer immunotherapy antibody aktivacija T celic imunoterapija raka protitelesa