Identification of the targets of T-cell receptor therapeutic agents and cells by use of a high-throughput genetic platform Journal Article
| Authors: | Gejman, R. S.; Jones, H. F.; Klatt, M. G.; Chang, A. Y.; Oh, C. Y.; Chandran, S. S.; Korontsvit, T.; Zakahleva, V.; Dao, T.; Klebanoff, C. A.; Scheinberg, D. A. |
| Article Title: | Identification of the targets of T-cell receptor therapeutic agents and cells by use of a high-throughput genetic platform |
| 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 MHC 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 immunologic assays and determines the reactivities of TCR-like therapeutic agents against large libraries of MHC-I ligands. In this article, we demonstrated that PresentER could be used to identify the on-and-off targets of T cells and TCR-mimic (TCRm) antibodies using in vitro coculture assays or binding assays. We found dozens of MHC-I ligands that were cross-reactive with two TCRm antibodies and two native TCRs and that were not easily predictable by other methods. ©2020 American Association for Cancer Research. |
| Journal Title: | Cancer Immunology Research |
| Volume: | 8 |
| Issue: | 5 |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2020-05-01 |
| Start Page: | 672 |
| End Page: | 684 |
| Language: | English |
| DOI: | 10.1158/2326-6066.Cir-19-0745 |
| PUBMED: | 32184297 |
| PROVIDER: | scopus |
| PMCID: | PMC7310334 |
| DOI/URL: | |
| Notes: | Viktoriya Zakahleva's name is misspelled on the original publication -- Article -- Source: Scopus |
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