Evidence map›Paper›PMID 32310221›Full record

ArticleThe Journal of clinical investigation2020

Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA.

Christopher J Holland, Rory M Crean, Johanne M Pentier, Ben de Wet, Angharad Lloyd, Velupillai Srikannathasan, Nikolai Lissin, Katy A Lloyd, Thomas H Blicher, Paul J Conroy and 19 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed.

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  13. An Engineered Soluble Single-Chain TCR Engager for KRAS-G12V Specific Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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  20. Review

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Christopher J HollandImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Rory M CreanDepartment of Biology and Biochemistry and.
Johanne M PentierImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Ben de WetImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Angharad LloydImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Velupillai SrikannathasanImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Nikolai LissinImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Katy A LloydImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Thomas H BlicherImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Paul J ConroyImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Miriam HockImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Robert J PengellyImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Thomas E SpinnerImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Brian CameronImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Elizabeth A PotterImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Anitha JeyanthanImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Peter E MolloyImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Malkit SamiImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Milos AleksicImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Nathaniel LiddyImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Ross A RobinsonImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Stephen HarperImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Marco LeporeImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Chris R PudneyDepartment of Biology and Biochemistry and.
Marc W van der KampSchool of Biochemistry, University of Bristol, Bristol, United Kingdom.
Pierre J RizkallahCardiff University School of Medicine, Heath Park, Cardiff, United Kingdom.
Bent K JakobsenImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
Annelise VuidepotImmunocore Ltd., Milton Park, Abingdon, United Kingdom.
David K ColeImmunocore Ltd., Milton Park, Abingdon, United Kingdom.

Funding

Biotechnology and Biological Sciences Research Council BB/M026280/1
6 · The paper itself

Abstract

Tumor-associated peptide-human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface-expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.

Indexed as

Amino Acid SequenceAntibodies, BispecificAntibodies, NeoplasmAntibody SpecificityAntigens, NeoplasmCell LineCell Line, TumorCrystallography, X-RayHLA AntigensHumansIndicators and ReagentsModels, MolecularMolecular Dynamics SimulationMolecular MimicryPeptidesReceptors, Antigen, T-CellAntibodies, BispecificAntibodies, NeoplasmAntigens, NeoplasmHLA AntigensIndicators and ReagentsPeptidesReceptors, Antigen, T-CellAntigen presentationCancer immunotherapyImmunologyStructural biologyTherapeutics

Identifiers

PMID32310221
PMCPMC7190993

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.