Evidence map›Paper›PMID 37488375›Full record

ArticleNature chemistry2023

Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer.

Peter A Szijj, Melissa A Gray, Mikaela K Ribi, Calise Bahou, João C F Nogueira, Carolyn R Bertozzi, Vijay Chudasama

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

27 citing papers in PubMed, 37 citations in OpenAlex.

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  19. Engaging T cells for cleanup.Frontiers in immunology · 2025
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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

7 authors at 2 institutions in 2 countries.

Peter A SzijjDepartment of Chemistry, University College London, London, UK.ORCID 0000-0002-2944-2676
Melissa A Gray *Department of Chemistry, Sarafan ChEM-H, and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Mikaela K Ribi *Department of Chemistry, Sarafan ChEM-H, and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6816-8326
Calise BahouDepartment of Chemistry, University College London, London, UK.
João C F NogueiraDepartment of Chemistry, University College London, London, UK.ORCID 0000-0002-5992-5900
Carolyn R BertozziDepartment of Chemistry, Sarafan ChEM-H, and Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. bertozzi@stanford.edu.ORCID 0000-0003-4482-2754
Vijay ChudasamaDepartment of Chemistry, University College London, London, UK. v.chudasama@ucl.ac.uk.ORCID 0000-0002-8876-3285
University College London · GBHoward Hughes Medical Institute · US

Funding

Targeting the Cancer GlycocalyxR01CA227942 · NCI · STANFORD UNIVERSITY · PI Carolyn Bertozzi · 2019 to 2026
$3.6M
Stanford ChEM-H Chemistry/Biology Interface Predoctoral Training ProgramT32GM139791 · NIGMS · STANFORD UNIVERSITY · PI Carolyn Bertozzi, Christine Jacobs-Wagner · 2021 to 2026
$2.4M
NCI NIH HHS R01 CA227942NIGMS NIH HHS T32 GM139791Wellcome Trust
6 · The paper itself

Abstract

Bispecific T cell engagers (BiTEs), a subset of bispecific antibodies (bsAbs), can promote a targeted cancer cell's death by bringing it close to a cytotoxic T cell. Checkpoint inhibitory T cell engagers (CiTEs) comprise a BiTE core with an added immunomodulatory protein, which serves to reverse cancer-cell immune-dampening strategies, improving efficacy. So far, protein engineering has been the main approach to generate bsAbs and CiTEs, but improved chemical methods for their generation have recently been developed. Homogeneous fragment-based bsAbs constructed from fragment antigen-binding regions (Fabs) can be generated using click chemistry. Here we describe a chemical method to generate biotin-functionalized three-protein conjugates, which include two CiTE molecules, one containing an anti-PD-1 Fab and the other containing an immunomodulatory enzyme, Salmonella typhimurium sialidase. The CiTEs' efficacy was shown to be superior to that of the simpler BiTE scaffold, with the sialidase-containing CiTE inducing substantially enhanced T cell-mediated cytotoxicity in vitro. The chemical method described here, more generally, enables the generation of multi-protein constructs with further biological applications.

Indexed as

Antibodies, BispecificNeoplasmsHumansNeuraminidaseProtein EngineeringT-LymphocytesAntibodies, BispecificNeuraminidase

Identifiers

PMID37488375
PMCPMC10624612
OpenAlexW4385224214

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.