Evidence map›Paper›PMID 38839891›Full record

ArticleCancer gene therapy2024

Integrating system biology and intratumor gene therapy by trans-complementing the appropriate co-stimulatory molecule as payload in oncolytic herpes virus.

A Finizio, P Pagano, A Napolano, G Froechlich, L Infante, A De Chiara, S Amiranda, E Vitiello, S Totaro, C Capasso and 5 more

Abstract read
In one paragraph

Article in Cancer gene therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

15 authors.

A Finizio *Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
P Pagano *Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
A NapolanoDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
G FroechlichDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
L InfanteNouscom S.R.L., Rome, Italy.
A De ChiaraDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
S AmirandaDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
E VitielloDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
S TotaroDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
C CapassoDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
M RaiaCEINGE Biotecnologie Avanzate Franco Salvatore S.C.aR.L., Naples, Italy.
A M D'AliseNouscom S.R.L., Rome, Italy.
P de CandiaDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
N ZambranoDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy.
E SassoDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Pansini 5, 80131, Napoli, NA, Italy. emanuele.sasso@unina.it.ORCID 0000-0002-6454-2824

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Systems biology has been applied at the multi-scale level within the cancer field, improving cancer prevention, diagnosis and enabling precision medicine approaches. While systems biology can expand the knowledge and skills for oncological treatment, it also represents a challenging expedition due to cancer complexity, heterogeneity and diversity not only between different cancer indications, but also in its evolution process through space and time. Here, by characterizing the transcriptional perturbations of the tumor microenvironment induced by oncolytic, we aimed to rationally design a novel armed oncolytic herpes virus. We found that intratumor oncovirotherapy with HSV-1 induces T-cell activation signatures and transcriptionally activates several costimulatory molecules. We identified differentially expressed costimulatory receptors and binding partners, where inducible co-stimulators (ICOS) resulted in the potentially most beneficial targeted therapy. Through an ex-vivo transcriptomic analysis, we explored the potential of arming an oncolytic virus as a combination therapy strategy; in particular, we engineered a targeted herpes virus encoding ICOSL (THV_ICOSL), which resulted in a significant improvement in tumor size control compared to unarmed parental virus. Also, combination with a PD-1 inhibitor enhanced antitumor efficacy as predictable by upregulation of PD-1 and ligands pair (PD-L1/PD-L2) upon oncolytic virus injection. Generation of the human version of this virus encoding hICOSL orthologue effectively and specifically activated human T cells by triggering the ICOS pathway. Our data support the data-driven generation of armed oncolytic viruses as combination immunotherapeutic with checkpoint inhibitors.

Indexed as

Genetic TherapyOncolytic VirotherapyOncolytic VirusesAnimalsCell Line, TumorFemaleHerpesvirus 1, HumanHumansMiceNeoplasmsSystems BiologyTumor Microenvironment

Identifiers

PMID38839891
PMCPMC11405262

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Registered trials

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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.