Evidence map›Paper›PMID 39112670›Full record

ArticleCancer immunology, immunotherapy : CII2024

NKG2D-bispecific enhances NK and CD8+ T cell antitumor immunity.

Aurelie Herault, Judy Mak, Josefa de la Cruz-Chuh, Michael A Dillon, Diego Ellerman, MaryAnn Go, Ely Cosino, Robyn Clark, Emily Carson, Stacey Yeung and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Second signals for cancer immunotherapy.Journal for immunotherapy of cancer · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
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

29 authors.

Aurelie HeraultDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA.
Judy MakDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA.
Josefa de la Cruz-ChuhDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Michael A DillonDepartment of Antibody Engineering, Genentech, South San Francisco, CA, USA.
Diego EllermanDepartment of Antibody Engineering, Genentech, South San Francisco, CA, USA.
MaryAnn GoDepartment of In Vivo Pharmacology, Genentech, South San Francisco, CA, USA.
Ely CosinoDepartment of In Vivo Pharmacology, Genentech, South San Francisco, CA, USA.
Robyn ClarkDepartment of In Vivo Pharmacology, Genentech, South San Francisco, CA, USA.
Emily CarsonDepartment of In Vivo Pharmacology, Genentech, South San Francisco, CA, USA.
Stacey YeungDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA.
Melanie PicheryImmuno-Oncology-In Vitro Biology Department, Evotec, Toulouse, France.
Mylène GadorImmuno-Oncology-In Vitro Biology Department, Evotec, Toulouse, France.
Eugene Y ChiangDepartment of Cancer Immunology, Genentech, South San Francisco, CA, USA.
Jia WuDepartment of Antibody Discovery, Genentech, South San Francisco, CA, USA.
Yuxin LiangDepartment of Next-GenSequencing, South San Francisco, CA, USA.
Zora ModrusanDepartment of Next-GenSequencing, South San Francisco, CA, USA.
Gautham GampaDepartment of Development Sciences PTPK, Genentech, South San Francisco, CA, USA.
Jawahar SudhamsuDepartment of Structural Biology, Genentech, South San Francisco, CA, USA.
Christopher C KemballDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Victoria CheungDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA.
Thi Thu Thao NguyenDepartment of Bioinformatics, Genentech, South San Francisco, CA, USA.
Dhaya SeshasayeeDepartment of Antibody Discovery, Genentech, South San Francisco, CA, USA.
Robert PiskolDepartment of Bioinformatics, Genentech, South San Francisco, CA, USA.
Klara TotpalDepartment of In Vivo Pharmacology, Genentech, South San Francisco, CA, USA.
Shang-Fan YuDepartment of In Vivo Pharmacology, Genentech, South San Francisco, CA, USA.
Genee LeeDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA.
Katherine R KozakDepartment of Biochemical and Cellular Pharmacology, Genentech, South San Francisco, CA, USA.
Christoph SpiessDepartment of Antibody Engineering, Genentech, South San Francisco, CA, USA.
Kevin B WalshDepartment of Molecular Oncology, Genentech, South San Francisco, CA, USA. walshk6@gene.com.ORCID http://orcid.org/0000-0003-1887-7647

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCancer immunotherapy approaches that elicit immune cell responses, including T and NK cells, have revolutionized the field of oncology. However, immunosuppressive mechanisms restrain immune cell activation within solid tumors so additional strategies to augment activity are required.

methodsWe identified the co-stimulatory receptor NKG2D as a target based on its expression on a large proportion of CD8+ tumor infiltrating lymphocytes (TILs) from breast cancer patient samples. Human and murine surrogate NKG2D co-stimulatory receptor-bispecifics (CRB) that bind NKG2D on NK and CD8+ T cells as well as HER2 on breast cancer cells (HER2-CRB) were developed as a proof of concept for targeting this signaling axis in vitro and in vivo.

resultsHER2-CRB enhanced NK cell activation and cytokine production when co-cultured with HER2 expressing breast cancer cell lines. HER2-CRB when combined with a T cell-dependent-bispecific (TDB) antibody that synthetically activates T cells by crosslinking CD3 to HER2 (HER2-TDB), enhanced T cell cytotoxicity, cytokine production and in vivo antitumor activity. A mouse surrogate HER2-CRB (mHER2-CRB) improved in vivo efficacy of HER2-TDB and augmented NK as well as T cell activation, cytokine production and effector CD8+ T cell differentiation.

conclusionWe demonstrate that targeting NKG2D with bispecific antibodies (BsAbs) is an effective approach to augment NK and CD8+ T cell antitumor immune responses. Given the large number of ongoing clinical trials leveraging NK and T cells for cancer immunotherapy, NKG2D-bispecifics have broad combinatorial potential.

Indexed as

Breast NeoplasmsCD8-Positive T-LymphocytesKiller Cells, NaturalNK Cell Lectin-Like Receptor Subfamily KAnimalsCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleHumansImmunotherapyLymphocyte ActivationLymphocytes, Tumor-InfiltratingMiceERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesKLRK1 protein, humanNK Cell Lectin-Like Receptor Subfamily KBispecificsCD8+ T cellsNK cellsNKG2DSynthetic immunity

Identifiers

PMID39112670
PMCPMC11306676

What OpenQuestion 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 OpenQuestion graph.