Evidence map›Paper›PMID 35013574›Full record

ArticleNature biomedical engineering2022

Intratumourally injected alum-tethered cytokines elicit potent and safer local and systemic anticancer immunity.

Yash Agarwal, Lauren E Milling, Jason Y H Chang, Luciano Santollani, Allison Sheen, Emi A Lutz, Anthony Tabet, Jordan Stinson, Kaiyuan Ni, Kristen A Rodrigues and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature biomedical engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
10.6field-weighted citation impact, top 1% 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

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

  1. Pooled it
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  5. Covalent tumor anchoring spatially orchestrates antitumor immunity.bioRxiv : the preprint server for biology · 2026
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20 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

14 authors at 5 institutions in 1 country.

Yash AgarwalDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7785-7828
Lauren E MillingDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jason Y H ChangKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2238-8232
Luciano SantollaniKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Allison SheenDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Emi A LutzDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7649-4241
Anthony TabetKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jordan StinsonDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kaiyuan NiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kristen A RodriguesKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0680-9834
Tyson J MoyerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Mariane B MeloKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0409-2454
Darrell J IrvineDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. djirvine@mit.edu.ORCID http://orcid.org/0000-0002-8637-1405
K Dane WittrupDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. wittrup@mit.edu.ORCID http://orcid.org/0000-0003-2398-5896
Massachusetts Institute of Technology · USRagon Institute of MGH, MIT and Harvard · USIIT@MIT · USInternational AIDS Vaccine Initiative · USScripps Research Institute · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
Localized immunotherapy using alum-binding therapeuticsR01EB031082 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IRVINE, DARRELL J, WITTRUP, KARL DANE · 2021 to 2024
$2.1M
Intratumoral Cytokine Immunotherapy Studies in Companion Canine Cancer ModelsR01CA271243 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI FAN, TIMOTHY M, WITTRUP, KARL DANE · 2022 to 2025
$2.0M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NCI NIH HHS R01 CA271243NIBIB NIH HHS R01 EB031082
6 · The paper itself

Abstract

Anti-tumour inflammatory cytokines are highly toxic when administered systemically. Here, in multiple syngeneic mouse models, we show that the intratumoural injection of recombinantly expressed cytokines bound tightly to the common vaccine adjuvant aluminium hydroxide (alum) (via ligand exchange between hydroxyls on the surface of alum and phosphoserine residues tagged to the cytokine by an alum-binding peptide) leads to weeks-long retention of the cytokines in the tumours, with minimal side effects. Specifically, a single dose of alum-tethered interleukin-12 induced substantial interferon-γ-mediated T-cell and natural-killer-cell activities in murine melanoma tumours, increased tumour antigen accumulation in draining lymph nodes and elicited robust tumour-specific T-cell priming. Moreover, intratumoural injection of alum-anchored cytokines enhanced responses to checkpoint blockade, promoting cures in distinct poorly immunogenic syngeneic tumour models and eliciting control over metastases and distant untreated lesions. Intratumoural treatment with alum-anchored cytokines represents a safer and tumour-agnostic strategy to improving local and systemic anticancer immunity.

Indexed as

Alum CompoundsCytokinesAnimalsImmunotherapyInterleukin-12MiceAlum Compoundsaluminum sulfateCytokinesInterleukin-12

Identifiers

PMID35013574
PMCPMC9681025
OpenAlexW4205511360

What OpenQuestion holds

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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.