Evidence map›Paper›PMID 39160299›Full record

ArticleNPJ precision oncology2024

A synthetic cytotoxic T cell platform for rapidly prototyping TCR function.

Govinda Sharma, James Round, Fei Teng, Zahra Ali, Chris May, Eric Yung, Robert A Holt

Abstract read
In one paragraph

Article in NPJ precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Govinda SharmaMichael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0002-5675-2637
James RoundMichael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada.
Fei TengMichael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada.
Zahra AliMichael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada.
Chris MayMichael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada.
Eric YungMichael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada.
Robert A HoltMichael Smith Genome Sciences Centre, British Columbia Cancer Research Institute, Vancouver, BC, Canada. rholt@bcgsc.ca.ORCID http://orcid.org/0000-0002-7259-1247

Funding

Analysis of T-cell antigen diversity by deep sequencingR21CA226321 · NCI · PROVINCIAL HEALTH SERVICES AUTHORITY · PI HOLT, ROBERT ANDREW · 2018 to 2019
$209k
Genome British Columbia PIF005Michael Smith Foundation for Health Research (MSFHR) I2C2020Michael Smith Foundation for Health Research (MSFHR) I2C2021NCI NIH HHS R21 CA226321U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R21CA226321-01
6 · The paper itself

Abstract

Current tools for functionally profiling T cell receptors with respect to cytotoxic potency and cross-reactivity are hampered by difficulties in establishing model systems to test these proteins in the contexts of different HLA alleles and against broad arrays of potential antigens. We have implemented a granzyme-activatable sensor of T cell cytotoxicity in a universal prototyping platform which enables facile recombinant expression of any combination of TCR-, peptide-, and class I MHC-coding sequences and direct assessment of resultant responses. This system consists of an engineered cell platform based on the immortalized natural killer cell line, YT-Indy, and the MHC-null antigen-presenting cell line, K562. These cells were engineered to furnish the YT-Indy/K562 pair with appropriate protein domains required for recombinant TCR expression and function in a non-T cell chassis, integrate a fluorescence-based target-centric early detection reporter of cytotoxic function, and deploy a set of protective genetic interventions designed to preserve antigen-presenting cells for subsequent capture and downstream characterization. Our data show successful reconstitution of the surface TCR complex in the YT-Indy cell line at biologically relevant levels. We also demonstrate successful induction and highly sensitive detection of antigen-specific response in multiple distinct model TCRs. Additionally, we monitored destruction of targets in co-culture and found that our survival-optimized system allowed for complete preservation after 24 h exposure to cytotoxic effectors. With this bioplatform, we anticipate investigators will be empowered to rapidly express and characterize T cell receptor responses, generate knowledge regarding the patterns of T cell receptor recognition, and optimize therapeutic T cell receptors.

Identifiers

PMID39160299
PMCPMC11333705

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.