Evidence map›Paper›PMID 38631714›Full record

ArticleJournal for immunotherapy of cancer2024

Efficacy of LCMV-based cancer immunotherapies is unleashed by intratumoral injections of polyI:C.

Celia Gomar, Claudia Augusta Di Trani, Angela Bella, Leire Arrizabalaga, Jose Gonzalez-Gomariz, Myriam Fernandez-Sendin, Maite Alvarez, Joan Salvador Russo-Cabrera, Nuria Ardaiz, Fernando Aranda and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
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  4. The role of ADAR1 in human pathophysiology.Frontiers in cell and developmental biology · 2025
    Review
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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

16 authors at 3 institutions in 1 country.

Celia GomarProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Claudia Augusta Di TraniProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Angela BellaProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Leire ArrizabalagaProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Jose Gonzalez-GomarizProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Myriam Fernandez-SendinProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Maite AlvarezProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.ORCID 0000-0002-5969-9181
Joan Salvador Russo-CabreraProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Nuria ArdaizProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
Fernando ArandaProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.ORCID 0000-0002-9364-474X
Timo SchippersHookipa Pharma Inc, New York, New York, USA.
Marisol QuinteroHighlight Therapeutics, Valencia, Spain.
Ignacio MeleroProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.ORCID 0000-0002-1360-348X
Klaus K OrlingerHookipa Pharma Inc, New York, New York, USA.
Henning LauterbachHookipa Pharma Inc, New York, New York, USA.ORCID 0000-0002-6062-5163
Pedro BerraondoProgram of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain pberraondol@unav.es.ORCID 0000-0001-7410-1865
Universidad de Navarra · ESClinica Universidad de Navarra · ESHighlight Therapeutics (Spain) · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLymphocytic choriomeningitis virus (LCMV) belongs to the Arenavirus family known for inducing strong cytotoxic T-cell responses in both mice and humans. LCMV has been engineered for the development of cancer immunotherapies, currently undergoing evaluation in phase I/II clinical trials. Initial findings have demonstrated safety and an exceptional ability to activate and expand tumor-specific T lymphocytes. Combination strategies to maximize the antitumor effectiveness of LCMV-based immunotherapies are being explored.

methodsWe assessed the antitumor therapeutic effects of intratumoral administration of polyinosinic:polycytidylic acid (poly(I:C)) and systemic vaccination using an LCMV-vector expressing non-oncogenic versions of the E6 and E7 antigens of human papillomavirus 16 (artLCMV-E7E6) in a bilateral model engrafting TC-1/A9 cells. This cell line, derived from the parental TC-1, exhibits low MHC class I expression and is highly immune-resistant. The mechanisms underlying the combination's efficacy were investigated through bulk RNA-seq, flow cytometry analyses of the tumor microenvironment, selective depletions using antibodies and clodronate liposomes, Batf3 deficient mice, and in vivo bioluminescence experiments. Finally, we assessed the antitumor effectiveness of the combination of artLCMV-E7E6 with BO-112, a GMP-grade poly(I:C) formulated in polyethyleneimine, currently under evaluation in clinical trials.

resultsIntratumoral injection of poly(I:C) enhanced the antitumor efficacy of artLCMV-E7E6 in both injected and non-injected tumor lesions. The combined treatment resulted in a significant delay in tumor growth and often complete eradication of several tumor lesions, leading to significantly improved survival compared with monotherapies. While intratumoral administration of poly(I:C) did not impact LCMV vector biodistribution or transgene expression, it significantly modified leucocyte infiltrates within the tumor microenvironment and amplified systemic efficacy through proinflammatory cytokines/chemokines such as CCL3, CCL5, CXCL10, TNF, IFNα, and IL12p70. Upregulation of MHC on tumor cells and a reconfiguration of the gene expression programs related to tumor vasculature, leucocyte migration, and the activation profile of tumor-infiltrating CD8

conclusionIntratumoral injection of poly(I:C) sensitizes MHC

Indexed as

Lymphocytic choriomeningitis virusNeoplasmsPoly I-CAdjuvants, ImmunologicAnimalsHumansImmunotherapyInjections, IntralesionalMiceTissue DistributionTumor MicroenvironmentAdjuvants, ImmunologicBO-112Poly I-CAdjuvants, ImmunologicDrug Evaluation, PreclinicalImmunogenicity, VaccineImmunotherapyVaccination

Identifiers

PMID38631714
PMCPMC11029445
OpenAlexW4394893374

What OpenQuestion holds

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LicenceCC BY-NC
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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.