Evidence map›Paper›PMID 27858101›Full record

ArticleCancer immunology, immunotherapy : CII2017

A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents.

Sylvia Herter, Laura Morra, Ramona Schlenker, Jitka Sulcova, Linda Fahrni, Inja Waldhauer, Steffi Lehmann, Timo Reisländer, Irina Agarkova, Jens M Kelm and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 2 pooled it
4.7field-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

73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
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  6. Article
  7. Review
  8. Advances and challenges in human 3D solid tumor models.Advanced functional materials · 2025
    Article
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  18. Review
  19. 3D cancer models: One step closer toFrontiers in immunology · 2023
    Review
  20. Frontiers in immunology · 2023
    Review

13 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

13 authors at 2 institutions in 1 country.

Sylvia HerterRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Laura MorraRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Ramona SchlenkerInstitute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland.
Jitka SulcovaRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Linda FahrniRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Inja WaldhauerRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Steffi LehmannRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Timo ReisländerRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Irina AgarkovaInSphero AG, Wagistrasse 27, 8952, Schlieren, Switzerland.
Jens M KelmInSphero AG, Wagistrasse 27, 8952, Schlieren, Switzerland.
Christian KleinRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Pablo UmanaRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland.
Marina BacacRoche Pharmaceutical Research and Early Development, Oncology DTA, Roche Innovation Center Zurich, Wagistrasse 18, 8952, Schlieren, Switzerland. marina.bacac@roche.com.
Roche (Switzerland) · CHUniversity Hospital of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The complexity of the tumor microenvironment is difficult to mimic in vitro, particularly regarding tumor-host interactions. To enable better assessment of cancer immunotherapy agents in vitro, we developed a three-dimensional (3D) heterotypic spheroid model composed of tumor cells, fibroblasts, and immune cells. Drug targeting, efficient stimulation of immune cell infiltration, and specific elimination of tumor or fibroblast spheroid areas were demonstrated following treatment with a novel immunocytokine (interleukin-2 variant; IgG-IL2v) and tumor- or fibroblast-targeted T cell bispecific antibody (TCB). Following treatment with IgG-IL2v, activation of T cells, NK cells, and NKT cells was demonstrated by increased expression of the activation marker CD69 and enhanced cytokine secretion. The combination of TCBs with IgG-IL2v molecules was more effective than monotherapy, as shown by enhanced effects on immune cell infiltration; activation; increased cytokine secretion; and faster, more efficient elimination of targeted cells. This study demonstrates that the 3D heterotypic spheroid model provides a novel and versatile tool for in vitro evaluation of cancer immunotherapy agents and allows for assessment of additional aspects of the activity of cancer immunotherapy agents, including analysis of immune cell infiltration and drug targeting.

Indexed as

AnimalsHumansImmunotherapyNeoplasmsSpheroids, CellularTumor Microenvironment3D modelCancer immunotherapyHeterotypic spheroid modelInterleukin-2 immunocytokine fusionT cell bispecific antibodiesTumor–stroma interaction

Identifiers

PMID27858101
PMCPMC5222939
OpenAlexW2550597146

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.