Evidence map›Paper›PMID 33925968›Full record

ArticleCells2021

In Vitro Evaluation of CD276-CAR NK-92 Functionality, Migration and Invasion Potential in the Presence of Immune Inhibitory Factors of the Tumor Microenvironment.

Stefan Grote, Guillermo Ureña-Bailén, Kenneth Chun-Ho Chan, Caroline Baden, Markus Mezger, Rupert Handgretinger, Sabine Schleicher

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.7field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 36 citations in OpenAlex.

  1. Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026
    Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025
    Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. CRISPR-Cas9-Based Gene Knockout of Immune Checkpoints in Expanded NK Cells.International journal of molecular sciences · 2023
    Article
  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

7 authors at 1 institution in 1 country.

Stefan GroteDepartment of Hematology and Oncology, Children's Hospital, University Hospital Tuebingen, 72076 Tuebingen, Germany.ORCID 0000-0001-8713-6709
Guillermo Ureña-BailénDepartment of Hematology and Oncology, Children's Hospital, University Hospital Tuebingen, 72076 Tuebingen, Germany.
Kenneth Chun-Ho ChanDepartment of Hematology and Oncology, Children's Hospital, University Hospital Tuebingen, 72076 Tuebingen, Germany.
Caroline BadenDepartment of Hematology and Oncology, Children's Hospital, University Hospital Tuebingen, 72076 Tuebingen, Germany.
Markus MezgerDepartment of Hematology and Oncology, Children's Hospital, University Hospital Tuebingen, 72076 Tuebingen, Germany.ORCID 0000-0002-0211-2343
Rupert HandgretingerDepartment of Hematology and Oncology, Children's Hospital, University Hospital Tuebingen, 72076 Tuebingen, Germany.
Sabine SchleicherDepartment of Hematology and Oncology, Children's Hospital, University Hospital Tuebingen, 72076 Tuebingen, Germany.ORCID 0000-0002-1847-2984
University Children's Hospital Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMelanoma is the most lethal of all skin-related cancers with incidences continuously rising. Novel therapeutic approaches are urgently needed, especially for the treatment of metastasizing or therapy-resistant melanoma. CAR-modified immune cells have shown excellent results in treating hematological malignancies and might represent a new treatment strategy for refractory melanoma. However, solid tumors pose some obstacles for cellular immunotherapy, including the identification of tumor-specific target antigens, insufficient homing and infiltration of immune cells as well as immune cell dysfunction in the immunosuppressive tumor microenvironment (TME).

methodsIn order to investigate whether CAR NK cell-based immunotherapy can overcome the obstacles posed by the TME in melanoma, we generated CAR NK-92 cells targeting CD276 (B7-H3) which is abundantly expressed in solid tumors, including melanoma, and tested their effectivity in vitro in the presence of low pH, hypoxia and other known factors of the TME influencing anti-tumor responses. Moreover, the CRISPR/Cas9-induced disruption of the inhibitory receptor NKG2A was assessed for its potential enhancement of NK-92-mediated anti-tumor activity.

resultsCD276-CAR NK-92 cells induced specific cytolysis of melanoma cell lines while being able to overcome a variety of the immunosuppressive effects normally exerted by the TME. NKG2A knock-out did not further improve CAR NK-92 cell-mediated cytotoxicity.

conclusionsThe strong cytotoxic effect of a CD276-specific CAR in combination with an "off-the-shelf" NK-92 cell line not being impaired by some of the most prominent negative factors of the TME make CD276-CAR NK-92 cells a promising cellular product for the treatment of melanoma and beyond.

Indexed as

Gene Expression Regulation, NeoplasticTumor MicroenvironmentAntigens, NeoplasmB7 AntigensCell Line, TumorCell MovementCRISPR-Cas SystemsCytotoxicity, ImmunologicFibroblastsHumansHydrogen-Ion ConcentrationHypoxiaImmune SystemImmunosuppression TherapyImmunosuppressive AgentsImmunotherapy, AdoptiveAntigens, NeoplasmB7 AntigensCD276 protein, humanImmunosuppressive AgentsLactic AcidReceptors, Chimeric AntigenB7-H3CD276chimeric antigen receptorCRISPR/Cas9immune therapymelanomaNK-92

Identifiers

PMID33925968
PMCPMC8145105
OpenAlexW3158490785

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.