Evidence map›Paper›PMID 34953983›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2022

BiTE secretion from in situ-programmed myeloid cells results in tumor-retained pharmacology.

S Hao, V V Inamdar, E C Sigmund, F Zhang, S B Stephan, C Watson, S J Weaver, U B Nielsen, M T Stephan

Open access · hybridAbstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.6field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. In vivo CAR engineering for immunotherapy.Nature reviews. Immunology · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. 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

9 authors at 1 institution in 1 country.

S HaoClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
V V InamdarClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
E C SigmundClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
F ZhangClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
S B StephanClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
C WatsonComparative Pathology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
S J WeaverExperimental Histopathology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
U B NielsenTidal Therapeutics (A Sanofi Company), 270 Albany St, Cambridge, MA 02139, USA.
M T StephanClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Bioengineering and Molecular Engineering & Sciences Institute, University of Washington, Seattle 98195, WA, USA. Electronic address: mstephan@fredhutch.org.
Fred Hutch Cancer Center · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Developing macrophage reprogramming mRNA nanocarriers for initial clinical testingR01CA263524 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STEPHAN, MATTHIAS · 2021 to 2024
$2.7M
Rational in situ programming of cancer vaccine-responding T-cell clonesR01CA261858 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STEPHAN, MATTHIAS · 2021 to 2025
$2.3M
Generating rapid antitumor immunity with lymphocyte-reprogramming nanocarriersR01CA207407 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STEPHAN, MATTHIAS · 2017 to 2021
$1.8M
NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA207407NCI NIH HHS R01 CA261858NCI NIH HHS R01 CA263524
6 · The paper itself

Abstract

Bispecific T-Cell Engagers (BiTEs) are effective at inducing remission in hematologic cancers, but their use in solid tumors has been challenging due to their extreme potency and on-target, off-tumor toxicities in healthy tissue. Their deployment against solid tumors is further complicated by insufficient drug penetration, a hostile tumor microenvironment, and immune escape. To address these challenges, we developed targeted nanocarriers that can deliver in vitro-transcribed mRNA encoding BiTEs to host myeloid cells - a cell type that is actively recruited into the tumor microenvironment. We demonstrate in an immunocompetent mouse model of ovarian cancer, that infusion of these nanoparticles directs BiTE expression to tumor sites, which reshapes the microenvironment from suppressive to permissive and triggers disease regression without systemic toxicity. In contrast, conventional injections of recombinant BiTE protein at doses required to achieve anti-tumor activity, induced systemic inflammatory responses and severe tissue damage in all treated animals. Implemented in the clinic, this in situ gene therapy could enable physicians - with a single therapeutic - to safely target tumor antigen that would otherwise not be druggable due to the risks of on-target toxicity and, at the same time, reset the tumor milieu to boost key mediators of antitumor immune responses.

Indexed as

NeoplasmsTumor MicroenvironmentAnimalsDisease Models, AnimalMiceMyeloid CellsT-LymphocytesBi-specific T-cell engagers (BiTEs)In situ gene therapyNanotechnology

Identifiers

PMID34953983
PMCPMC8840964
OpenAlexW4200451376

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.