Evidence map›Paper›PMID 22916301›Full record

ArticlePloS one2012

T cell receptor-like recognition of tumor in vivo by synthetic antibody fragment.

Keith R Miller, Akiko Koide, Brenda Leung, Jonathan Fitzsimmons, Bryan Yoder, Hong Yuan, Michael Jay, Sachdev S Sidhu, Shohei Koide, Edward J Collins

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
6.0field-weighted citation impact, top 4% 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

79 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Engineering antibody-drug conjugates targeting an adhesion GPCR, CD97.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Article
  11. Generation of actionable, cancer-specific neoantigens from KRAS(G12C) with adagrasib.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Structural basis for nucleolin recognition ofScience (New York, N.Y.) · 2025
    Article
  18. Article
  19. Binding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article

19 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

10 authors at 4 institutions in 2 countries.

Keith R MillerDepartment of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina, USA.
Akiko Koide
Brenda Leung
Jonathan Fitzsimmons
Bryan Yoder
Hong Yuan
Michael Jay
Sachdev S Sidhu
Shohei Koide
Edward J Collins
University of North Carolina at Chapel Hill · USUniversity of Illinois Chicago · USUniversity of Chicago · USUniversity of Toronto · CA

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Chaperone Assisted CrystallographyR01GM072688 · NIGMS · UNIVERSITY OF CHICAGO · PI KOSSIAKOFF, ANTHONY A · 2005 to 2012
$2.7M
Heme Scavenging and Uptake by Haemophilus ducreyiR21AI088081 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COLLINS, EDWARD JOHN · 2010 to 2011
$405k
NCI NIH HHS P30 CA016086NCI NIH HHS P30CA06086NIAID NIH HHS AI088081NIAID NIH HHS P30 AI050410NIAID NIH HHS P30 AI50410NIAID NIH HHS R21 AI088081NIGMS NIH HHS R01 GM072688NIGMS NIH HHS R01-GM072688
6 · The paper itself

Abstract

A major difficulty in treating cancer is the inability to differentiate between normal and tumor cells. The immune system differentiates tumor from normal cells by T cell receptor (TCR) binding of tumor-associated peptides bound to Major Histocompatibility Complex (pMHC) molecules. The peptides, derived from the tumor-specific proteins, are presented by MHC proteins, which then serve as cancer markers. The TCR is a difficult protein to use as a recombinant protein because of production issues and has poor affinity for pMHC; therefore, it is not a good choice for use as a tumor identifier outside of the immune system. We constructed a synthetic antibody-fragment (Fab) library in the phage-display format and isolated antibody-fragments that bind pMHC with high affinity and specificity. One Fab, fE75, recognizes our model cancer marker, the Human Epidermal growth factor Receptor 2 (HER2/neu) peptide, E75, bound to the MHC called Human Leukocyte Antigen-A2 (HLA-A2), with nanomolar affinity. The fE75 bound selectively to E75/HLA-A2 positive cancer cell lines in vitro. The fE75 Fab conjugated with (64)Cu selectively accumulated in E75/HLA-A2 positive tumors and not in E75/HLA-A2 negative tumors in an HLA-A2 transgenic mouse as probed using positron emission tomography/computed tomography (PET/CT) imaging. Considering that hundreds to thousands of different peptides bound to HLA-A2 are present on the surface of each cell, the fact that fE75 arrives at the tumor at all shows extraordinary specificity. These antibody fragments have great potential for diagnosis and targeted drug delivery in cancer.

Indexed as

AnimalsCell Line, TumorCHO CellsCricetinaeErb-b2 Receptor Tyrosine KinasesHLA-A2 AntigenHumansImmunoglobulin FragmentsMicePeptidesProtein BindingReceptors, Antigen, T-CellErb-b2 Receptor Tyrosine KinasesHLA-A2 AntigenImmunoglobulin FragmentsPeptidesReceptors, Antigen, T-Cell

Identifiers

PMID22916301
PMCPMC3423377
OpenAlexW1983335488

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.