Evidence map›Paper›PMID 42128520›Full record

ArticleJournal for immunotherapy of cancer2026

Synthetic DNA vaccine platform elicits potent immunity where electroporated naked-mRNA is non-immunogenic.

Claudia Tonini, Andrea Bianchi, Mauro Esposito, Ilaria Esposito, Tiziano Giacomelli, Emily Young, Heikki Lanckriet, Zoe Whiffen, Milena Pavlickova, Deborah Entiriwaa and 10 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. Article
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

20 authors.

Claudia Tonini *Neomatrix, Rome, Italy.ORCID http://orcid.org/0000-0002-9979-1142
Andrea Bianchi *Neomatrix, Rome, Italy.ORCID http://orcid.org/0000-0002-0391-0945
Mauro EspositoNeomatrix, Rome, Italy.ORCID http://orcid.org/0000-0003-3826-8419
Ilaria EspositoNeomatrix, Rome, Italy.ORCID http://orcid.org/0000-0003-2784-8936
Tiziano GiacomelliNeomatrix, Rome, Italy.
Emily Young4basebio, Cambridge, UK.
Heikki Lanckriet4basebio, Cambridge, UK.
Zoe Whiffen4basebio, Cambridge, UK.
Milena Pavlickova4basebio, Cambridge, UK.
Deborah Entiriwaa4basebio, Cambridge, UK.
Eugenia PrincipatoTakis, Rome, Italy.
Giuseppe RoscilliTakis, Rome, Italy.ORCID http://orcid.org/0000-0002-0495-8668
Silvia PiconeseScienze Cliniche Internistiche, Anestestiologiche e Cardiovascolari, Sapienza University of Rome, Roma, Italy.ORCID http://orcid.org/0000-0002-9685-5227
Lucia LioneTakis, Rome, Italy.
Erika SalvatoriTakis, Rome, Italy.
Eleonora PintoTakis, Rome, Italy.
Gennaro CilibertoTakis, Rome, Italy.
Luigi AurisicchioNeomatrix, Rome, Italy.
Amy Walker4basebio, Cambridge, UK.
Fabio PalomboNeomatrix, Rome, Italy fabio.palombo@neomatrixbiotech.com.ORCID http://orcid.org/0000-0003-0473-4901

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors have transformed cancer therapy, yet many patients fail to respond, underscoring the need for complementary strategies. Personalized neoantigen cancer vaccines (NCVs), which stimulate highly specific T-cell responses against tumor-specific mutations, are a promising approach now advancing in clinical development.

methodsWe developed a clinically scalable platform based on high-purity linear hairpin DNA (hpDNA), produced by an entirely cell-free enzymatic method and delivered intramuscularly by electroporation (EP). An M20-hpDNA vaccine, encoding 20 neoantigens from the MC38 tumor model, was benchmarked against a plasmid DNA (pDNA) counterpart and a pseudouridine-modified messenger RNA (mRNA) version delivered by EP. Immune responses were characterized by enzyme-linked immunospot, flow cytometry, bulk RNA sequencing, and single-cell RNA/T-cell receptor sequencing. Antitumor activity was assessed in prophylactic, therapeutic, and metastatic mouse models.

resultshpDNA and pDNA vaccines elicited robust and comparable CD8

conclusionsThese findings demonstrate that hpDNA delivered by EP is a versatile, potent, and clinically scalable platform for personalized NCVs. Under the delivery conditions tested here, EP-delivered, non-formulated mRNA did not elicit detectable antigen-specific T-cell responses, whereas hpDNA induces productive inflammation and durable T-cell memory. These results highlight the importance of delivery context in shaping vaccine immunogenicity and support further development of hpDNA as a safe and competitive strategy for individualized cancer immunotherapy. Importantly, our data do not challenge the well-established immunogenicity and clinical activity of formulated mRNA vaccines (eg, mRNA-lipid nanoparticle) in infectious disease and cancer settings.

Indexed as

Cancer VaccinesElectroporationRNA, MessengerVaccines, DNAAnimalsAntigens, NeoplasmElectroporation TherapiesFemaleHumansMiceMice, Inbred C57BLAntigens, NeoplasmCancer VaccinesRNA, MessengerVaccines, DNAColon CancerImmunotherapyT cellVaccine

Identifiers

PMID42128520
PMCPMC13182474

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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.