Evidence map›Paper›PMID 37494434›Full record

ArticleScience advances2023

Multi-tiered approach to detect autoimmune cross-reactivity of therapeutic T cell receptors.

Kazusa Ishii, John S Davies, Andrew L Sinkoe, Kilyna A Nguyen, Scott M Norberg, Crystal P McIntosh, Tejas Kadakia, Carylinda Serna, Zachary Rae, Michael C Kelly and 1 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
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

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. PepGen: conditional generation of peptides for MHC binding.Bioinformatics (Oxford, England) · 2026
    Article
  2. Review
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  9. Identification of novel KRASJournal of translational medicine · 2025
    Article
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  11. Review
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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

11 authors at 4 institutions in 5 countries.

Kazusa IshiiCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0002-1915-6334
John S DaviesCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0002-9482-1066
Andrew L SinkoeCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0001-8311-1993
Kilyna A NguyenCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0001-7767-3260
Scott M NorbergCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0001-5232-2448
Crystal P McIntoshCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Tejas KadakiaCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Carylinda SernaCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Zachary RaeSingle Cell Analysis Facility, CCR, NCI, NIH, Bethesda, MD, USA.
Michael C KellySingle Cell Analysis Facility, CCR, NCI, NIH, Bethesda, MD, USA.ORCID 0000-0003-0654-2778
Christian S HinrichsCenter for Immuno-Oncology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0001-5597-2841
Center for Cancer Research · USAstraZeneca (Netherlands) · NLImpact Assessment · USMacmillan Cancer Support · GB

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
NCI NIH HHS 75N91019D00024
6 · The paper itself

Abstract

T cell receptor (TCR)-engineered T cell therapy using high-affinity TCRs is a promising treatment modality for cancer. Discovery of high-affinity TCRs especially against self-antigens can require approaches that circumvent central tolerance, which may increase the risk of cross-reactivity. Despite the potential for toxicity, no standardized approach to screen cross-reactivity has been established in the context of preclinical safety evaluation. Here, we describe a practical framework to prospectively detect clinically prohibitive cross-reactivity of therapeutic TCR candidates. Cross-reactivity screening consisted of multifaceted series of assays including assessment of p-MHC tetramer binding, cell line recognition, and reactivity against candidate peptide libraries. Peptide libraries were generated using conventional contact residue motif-guided search, amino acid substitution matrix-based search unguided by motif information, and combinatorial peptide library scan-guided search. We demonstrate the additive nature of a layered approach, which efficiently identifies unsafe cross-reactivity including one undetected by conventional motif-guided search. These findings have important implications for the safe development of TCR-based therapies.

Indexed as

Peptide LibraryReceptors, Antigen, T-CellPeptide LibraryReceptors, Antigen, T-Cell

Identifiers

PMID37494434
PMCPMC10371023
OpenAlexW4385281984

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.