ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026
CD8 co-receptor modulates the specificity profile of the 1G4 TCR against NY-ESO-1.
Heather F Jones, Zita E H Aretz, Ron S Gejman, Tara Cicic, David A Scheinberg
Abstract read
In one paragraphArticle in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
5 authors.
Heather F JonesPharmacology Program, Weill Cornell Medicine, New York, NY 10021, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Zita E H AretzPhysiology Biophysics and Systems Biology Program, Weill Cornell Medicine, New York, NY 10021, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ron S GejmanTri-Institutional MD-PhD Program, Sloan Kettering Institute, Weill Cornell Medicine and Rockefeller University, New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Tara CicicMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
David A ScheinbergPharmacology Program, Weill Cornell Medicine, New York, NY 10021, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: scheinbd@mskcc.org.
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MT LYMPHOCYTE SUBSET FUNCTION POST-TRANSPLANTATIONP01CA023766 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI O'REILLY, RICHARD JOHN · 1985 to 2023
$59.0MWeill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1MUnderstanding and Mimicking TCR Recognition with Therapeutic Monoclonal Antibodies.R35CA241894 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DAVID A SCHEINBERG · 2020 to 2026
$7.2MRECOMBINANT ANTICD33 ANTIBODY FOR AMLR01CA055349 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SCHEINBERG, DAVID A · 1991 to 2020
$6.8MImmunoediting in Human CancerF30CA200327 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI GEJMAN, RON S · 2015 to 2018
$187kA High Throughput Method to Determine the Target of T Cell ReceptorsF31CA253995 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI JONES, HEATHER · 2020 to 2021
$92kNCI NIH HHS F30 CA200327NCI NIH HHS F31 CA253995NCI NIH HHS P01 CA023766NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA055349NCI NIH HHS R35 CA241894NIGMS NIH HHS T32 GM007739
6 · The paper itselfAbstract
Engineered T cells have shown efficacy in cancer treatment. However, the promiscuity of TCR-engineered T cells may result in recognition of off-target epitopes, causing severe toxicities. A genetic screen of >3,000 proteomic epitopes in the MHCI ligandome uncovered off-target peptides for both, native and affinity-enhanced 1G4 TCR, which target cancer antigen NY-ESO-1/A02-expressing cells. We validated off-target peptides derived from the human proteome recognized by both TCRs, showing that the affinity-enhanced TCR has more off-targets. Multiple off-target epitopes were reactive only in CD8 T cells, not in CD4 T cells. We identified a previously undescribed class of CD8 receptor-dependent off-targets. CD8α-negative cells (CD8α
Indexed as
Antigens, NeoplasmCD8 AntigensMembrane ProteinsReceptors, Antigen, T-CellAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorEpitopes, T-LymphocyteHumansMiceAntigens, NeoplasmCD8 AntigensCTAG1B protein, humanEpitopes, T-LymphocyteMembrane ProteinsReceptors, Antigen, T-Cell1G4affinity-enhanced TCRcancer immunotherapyCD8 and CD4 rolesNY-ESO-1off-target reactivityPresentERT cell specificityTCR-engineered T cellstoxicity risks
Identifiers
PMID41058174
PMCPMC12590357
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