RT Journal Article
SR Electronic
T1 Identification of the targets of T cell receptor therapeutic agents and cells by use of a high throughput genetic platform
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 267047
DO 10.1101/267047
A1 Ron S. Gejman
A1 Heather F. Jones
A1 Martin G. Klat
A1 Aaron Y. Chang
A1 Claire Y. Oh
A1 Smita S. Chandran
A1 Tatiana Korontsvit
A1 Viktoriya Zakahleva
A1 Tao Dao
A1 Christopher A. Klebanoff
A1 David A. Scheinberg
YR 2018
UL http://biorxiv.org/content/early/2018/09/22/267047.abstract
AB T cell receptor (TCR)-based therapeutic cells and agents have emerged as a new class of effective cancer therapeutics. These therapies work on cells that express intracellular cancer-associated proteins by targeting peptides displayed on major histocompatibility complex receptors. However, cross-reactivities of these agents to off-target cells and tissues have resulted in serious, sometimes fatal, adverse events. We have developed a high throughput genetic platform (termed “PresentER”) that encodes MHC-I peptide minigenes for functional immunological assays as well as for determining the reactivities of TCR-like therapeutic agents against large libraries of MHC-I ligands. In this report, we demonstrate that PresentER can be used to identify the on-and-off targets of T cells and TCR mimic antibodies using in vitro co-culture assays or binding assays. We find dozens of MHC-I ligands that are cross-reactive with two TCR mimic antibodies and two native TCRs and that are not easily predictable by other methods.