Evidence map›Paper›PMID 29721366›Full record

ArticleOncoimmunology

TNFa and IL-2 armed adenoviruses enable complete responses by anti-PD-1 checkpoint blockade.

V Cervera-Carrascon, M Siurala, J M Santos, R Havunen, S Tähtinen, P Karell, S Sorsa, A Kanerva, A Hemminki

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05271318 (A Two-part, Phase I/Ib, Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus), which is not on this map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
11.6field-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.

NCT05271318 phase1 / phase2active not recruitingnot on this map

A Two-part, Phase I/Ib, Open-Label, Dose-escalation Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Combination With Pembrolizumab (Phase I Part) and Pembrolizumab and Pegylated Liposomal Doxorubicin (Phase Ib Part) in Patients With Platinum Resistant or Refractory Ovarian Cancer

TypeinterventionalSponsorTILT Biotherapeutics Ltd.Ran2022 to 2027Enrolled29ConditionsPlatinum-refractory Ovarian Carcinoma, Platinum-resistant Ovarian Cancer, Platinum-Resistant Fallopian Tube Carcinoma, Platinum-Resistant Primary Peritoneal CarcinomaArmsTILT-123, pembrolizumab, pegylated liposomal doxorubicin
3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 110 citations in OpenAlex.

  1. Oncoimmunology · 2026
    Article
  2. Review
  3. TNF-alpha: Roles in pathogenesis and therapeutics in cancer.The Journal of biological chemistry · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Construction and application of adenoviral vectors.Molecular therapy. Nucleic acids · 2023
    Review
  18. Review
  19. Article
  20. Review

16 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

9 authors at 1 institution in 1 country.

V Cervera-CarrasconTILT Biotherapeutics Ltd, Helsinki, Uusima, Finland.
M SiuralaTILT Biotherapeutics Ltd, Helsinki, Uusima, Finland.
J M SantosTILT Biotherapeutics Ltd, Helsinki, Uusima, Finland.
R HavunenTILT Biotherapeutics Ltd, Helsinki, Uusima, Finland.
S TähtinenDepartment of Oncology, Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Helsinki, Uusima, Finland.
P KarellInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Uusima, Finland.
S SorsaTILT Biotherapeutics Ltd, Helsinki, Uusima, Finland.
A KanervaDepartment of Oncology, Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Helsinki, Uusima, Finland.
A HemminkiTILT Biotherapeutics Ltd, Helsinki, Uusima, Finland.
University of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Releasing the patient's immune system against their own malignancy by the use of checkpoint inhibitors is delivering promising results. However, only a subset of patients currently benefit from them. One major limitation of these therapies relates to the inability of T cells to detect or penetrate into the tumor resulting in unresponsiveness to checkpoint inhibition. Virotherapy is an attractive tool for enabling checkpoint inhibitors as viruses are naturally recognized by innate defense elements which draws the attention of the immune system. Besides their intrinsic immune stimulating properties, the adenoviruses used here are armed to express tumor necrosis factor alpha (TNFa) and interleukin-2 (IL-2). These cytokines result in immunological danger signaling and multiple appealing T-cell effects, including trafficking, activation and propagation. When these viruses were injected into B16.OVA melanoma tumors in animals concomitantly receiving programmed cell-death protein 1 (PD-1) blocking antibodies both tumor growth control (p < 0.0001) and overall survival (p < 0.01) were improved. In this set-up, the addition of adoptive cell therapy with OT-I lymphocytes did not increase efficacy further. When virus injections were initiated before antibody treatment in a prime-boost approach, 100% of tumors regressed completely and all mice survived. Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells. These preclinical studies provide the rationale and schedule for a clinical trial where oncolytic adenovirus coding for TNFa and IL-2 (TILT-123) is used in melanoma patients receiving an anti-PD-1 antibody.

Indexed as

AdenovirusAdoptive cell therapyAdoptive T cell therapiesanti-PD1Checkpoint blockadeImmunotherapyImmunovirotherapyMelanomaModels of immunostimulationSolid tumorsT cell therapyTherapeutic antibodiesVirotherapy

Identifiers

PMID29721366
PMCPMC5927535
OpenAlexW2795176800

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.