Evidence map›Paper›PMID 32916097›Full record

ArticleCell systems2020

Discriminatory Power of Combinatorial Antigen Recognition in Cancer T Cell Therapies.

Ruth Dannenfelser, Gregory M Allen, Benjamin VanderSluis, Ashley K Koegel, Sarah Levinson, Sierra R Stark, Vicky Yao, Alicja Tadych, Olga G Troyanskaya, Wendell A Lim

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell systems, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing 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

67 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Spatial Regulation of CAR Signaling Enables Logic-Gated Activity.bioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. In vivo chimeric antigen receptor (CAR)-T cell therapy.Nature reviews. Drug discovery · 2026
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Ruth DannenfelserDepartment of Computer Science, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Gregory M AllenDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Cell Design Institute and Center for Synthetic Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Benjamin VanderSluisCenter for Computational Biology, Flatiron Institute, New York, NY 10010, USA.
Ashley K KoegelDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Cell Design Institute and Center for Synthetic Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; Division of Pediatric Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94158, USA.
Sarah LevinsonDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Sierra R StarkDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Cell Design Institute and Center for Synthetic Immunology, University of California, San Francisco, San Francisco, CA 94158, USA.
Vicky YaoDepartment of Computer Science, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Computer Science, Rice University, Houston, TX 77005, USA.
Alicja TadychLewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
Olga G TroyanskayaDepartment of Computer Science, Princeton University, Princeton, NJ 08540, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Center for Computational Biology, Flatiron Institute, New York, NY 10010, USA. Electronic address: ogt@genomics.princeton.edu.
Wendell A LimDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Cell Design Institute and Center for Synthetic Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: wendell.lim@ucsf.edu.

Funding

Quantitavie and Computational Biology Graduate ProgramT32HG003284 · NHGRI · PRINCETON UNIVERSITY · PI Joshua Michael Akey, Stanislav Y. Shvartsman · 2004 to 2026
$9.9M
User-control and safetyU54CA244438 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2019 to 2022
$7.8M
lntegration and Visualization of Diverse Biological DataR01GM071966 · NIGMS · PRINCETON UNIVERSITY · PI TROYANSKAYA, OLGA G · 2005 to 2022
$6.4M
Research Training in Childhood CancerT32CA128583 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Eric Alejandro Sweet-Cordero · 2007 to 2026
$6.0M
Redesigning the T cell: Using Synthetic Biology to Engineer Therapeutic CellsR01CA196277 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2014 to 2018
$3.3M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA196277NCI NIH HHS T32 CA128583NCI NIH HHS U54 CA244438NHGRI NIH HHS T32 HG003284NIGMS NIH HHS R01 GM071966
6 · The paper itself

Abstract

Precise discrimination of tumor from normal tissues remains a major roadblock for therapeutic efficacy of chimeric antigen receptor (CAR) T cells. Here, we perform a comprehensive in silico screen to identify multi-antigen signatures that improve tumor discrimination by CAR T cells engineered to integrate multiple antigen inputs via Boolean logic, e.g., AND and NOT. We screen >2.5 million dual antigens and ∼60 million triple antigens across 33 tumor types and 34 normal tissues. We find that dual antigens significantly outperform the best single clinically investigated CAR targets and confirm key predictions experimentally. Further, we identify antigen triplets that are predicted to show close to ideal tumor-versus-normal tissue discrimination for several tumor types. This work demonstrates the potential of 2- to 3-antigen Boolean logic gates for improving tumor discrimination by CAR T cell therapies. Our predictions are available on an interactive web server resource (antigen.princeton.edu).

Indexed as

Antigens, NeoplasmHumansImmunotherapy, AdoptiveAntigens, NeoplasmAND gateCAR T cellcombinatorial antigen recognitionNOT gateT cell therapeuticstumor antigenstumor-versus-normal discrimination

Identifiers

PMID32916097
PMCPMC7814417

What OpenQuestion holds

Textmetadata
LicenceTDM
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.