Evidence map›Paper›PMID 36162918›Full record

ArticleJournal for immunotherapy of cancer2022

TEM8 Tri-specific Killer Engager binds both tumor and tumor stroma to specifically engage natural killer cell anti-tumor activity.

Michael F Kaminski, Laura Bendzick, Rachel Hopps, Marissa Kauffman, Behiye Kodal, Yvette Soignier, Peter Hinderlie, Joshua T Walker, Todd R Lenvik, Melissa A Geller and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

18 citing papers in PubMed, 19 citations in OpenAlex.

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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

12 authors at 1 institution in 2 countries.

Michael F KaminskiHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Laura BendzickObstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Rachel HoppsObstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Marissa KauffmanHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Behiye KodalHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Yvette SoignierHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Peter HinderlieHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Joshua T WalkerHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Todd R LenvikHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Melissa A GellerObstetrics, Gynecology and Women's Health, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Jeffrey S MillerHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.
Martin FelicesHematology, Oncology, and Transplantation, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA mfelices@umn.edu.ORCID 0000-0002-5945-0634
University of Minnesota · US

Funding

Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Therapeutic Potential of Adaptive NK Cells in Cancer and TransplantationP01CA111412 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MILLER, JEFFREY S. · 2005 to 2025
$38.2M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
Viral priming and targeting NK cells against solid tumor malignanciesR35CA197292 · NCI · UNIVERSITY OF MINNESOTA · PI MILLER, JEFFREY S. · 2015 to 2021
$6.2M
NCATS NIH HHS UL1 TR002494NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA111412NCI NIH HHS R35 CA197292
6 · The paper itself

Abstract

backgroundThe tumor microenvironment contains stromal cells, including endothelial cells and fibroblasts, that aid tumor growth and impair immune cell function. Many solid tumors remain difficult to cure because of tumor-promoting stromal cells, but current therapies targeting tumor stromal cells are constrained by modest efficacy and toxicities. TEM8 is a surface antigen selectively upregulated on tumor and tumor stromal cells, endothelial cells and fibroblasts that may be targeted with specific natural killer (NK) cell engagement.

methodsA Tri-specific Killer Engager (TriKE) against TEM8-'cam1615TEM8'-was generated using a mammalian expression system. Its function on NK cells was assessed by evaluation of degranulation, inflammatory cytokine production, and killing against tumor and stroma cell lines in standard co-culture and spheroid assays. cam1615TEM8-mediated proliferation and STAT5 phosphorylation in NK cells was tested and compared with T cells by flow cytometry. NK cell proliferation, tumor infiltration, and tumor and tumor-endothelium killing by cam1615TEM8 and interleukin-15 (IL-15) were assessed in NOD scid gamma (NSG) mice.

resultscam1615TEM8 selectively stimulates NK cell degranulation and inflammatory cytokine production against TEM8-expressing tumor and stromal cell lines. The increased activation translated to superior NK cell killing of TEM8-expressing tumor spheroids. cam1615TEM8 selectively stimulated NK cell but not T cell proliferation in vitro and enhanced NK cell proliferation, survival, and tumor infiltration in vivo. Finally, cam1615TEM8 stimulated NK cell killing of tumor and tumor endothelial cells in vivo.

conclusionsOur findings indicate that the cam1615TEM8 TriKE is a novel anti-tumor, anti-stroma, and anti-angiogenic cancer therapy for patients with solid tumors. This multifunctional molecule works by selectively targeting and activating NK cells by costimulation with IL-15, and then targeting that activity to TEM8+ tumor cells and TEM8+ tumor stroma.

Indexed as

Interleukin-15NeoplasmsAnimalsAntigens, SurfaceEndothelial CellsKiller Cells, NaturalMammalsMiceMice, Inbred NODMice, SCIDMicrofilament ProteinsReceptors, Cell SurfaceSTAT5 Transcription FactorTumor MicroenvironmentAntigens, SurfaceInterleukin-15Microfilament ProteinsReceptors, Cell SurfaceSTAT5 Transcription FactorImmunotherapyKiller Cells, NaturalTumor Microenvironment

Identifiers

PMID36162918
PMCPMC9516302
OpenAlexW4297141578

What OpenQuestion holds

Textmetadata
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.