Format

Send to

Choose Destination
Cancer Immunol Res. 2020 Mar 17. pii: canimm.0745.2019. doi: 10.1158/2326-6066.CIR-19-0745. [Epub ahead of print]

Identification of the targets of T cell receptor therapeutic agents and cells by use of a high throughput genetic platform.

Author information

1
Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center.
2
Molecular Pharmacology, Memorial Sloan Kettering Cancer Center.
3
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center.
4
Memorial Sloan Kettering Cancer Center.
5
Molecular Pharmacology and Chemistry, Sloan Kettering Institute.
6
Molecular Pharmacology & Chemistry Program, Memorial Sloan Kettering Cancer Center.
7
Center for Cell Engineering, Memorial Sloan Kettering Cancer Center.
8
Molecular Pharmacology and Chemistry, Sloan Kettering Institute scheinbd@mskcc.org.

Abstract

T cell receptor (TCR)-based therapeutic cells and agents have emerged as a new class of effective cancer therapies. 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 and determines the reactivities of TCR-like therapeutic agents against large libraries of MHC-I ligands. In this report, we demonstrated that PresentER could 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 found dozens of MHC-I ligands that were cross-reactive with two TCR mimic antibodies and two native TCRs and that were not easily predictable by other methods.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center