Evidence map›Paper›PMID 33276580›Full record

ArticleBiomedicines2020

Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity.

Noelia Silva-Pilipich, Eva Martisova, María Cristina Ballesteros-Briones, Sandra Hervas-Stubbs, Noelia Casares, Gualberto González-Sapienza, Cristian Smerdou, Lucia Vanrell

Abstract read
In one paragraph

Article in Biomedicines, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Review
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  5. Targeting PD-1Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  6. Review
  7. 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

8 authors.

Noelia Silva-PilipichDivision of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, 31008 Pamplona, Spain.
Eva MartisovaDivision of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, 31008 Pamplona, Spain.
María Cristina Ballesteros-BrionesDivision of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, 31008 Pamplona, Spain.
Sandra Hervas-StubbsInstituto de Investigación Sanitaria de Navarra (IdISNA), 31008 Pamplona, Spain.ORCID 0000-0003-3391-1516
Noelia CasaresInstituto de Investigación Sanitaria de Navarra (IdISNA), 31008 Pamplona, Spain.
Gualberto González-SapienzaCátedra de Inmunología, DEPBIO, Facultad de Química, Instituto de Higiene, UDELAR, 11600 Montevideo, Uruguay.
Cristian SmerdouDivision of Gene Therapy and Regulation of Gene Expression, Cima Universidad de Navarra, 31008 Pamplona, Spain.
Lucia VanrellCátedra de Inmunología, DEPBIO, Facultad de Química, Instituto de Higiene, UDELAR, 11600 Montevideo, Uruguay.

Funding

Agencia Nacional de Investigación e Innovación 171/2014Agencia Nacional de Investigación e Innovación FMV_3_2016_1_125880Departamento de Salud, Gobierno de Navarra 64/2019Instituto de Salud Carlos III PI17/01859
6 · The paper itself

Abstract

Immune checkpoint blockade using monoclonal antibodies (mAbs) able to block programmed death-1 (PD-1)/PD-L1 axis represents a promising treatment for cancer. However, it requires repetitive systemic administration of high mAbs doses, often leading to adverse effects. We generated a novel nanobody against PD-1 (Nb11) able to block PD-1/PD-L1 interaction for both mouse and human molecules. Nb11 was cloned into an adeno-associated virus (AAV) vector downstream of four different promoters (CMV, CAG, EF1α, and SFFV) and its expression was analyzed in cells from rodent (BHK) and human origin (Huh-7). Nb11 was expressed at high levels in vitro reaching 2-20 micrograms/mL with all promoters, except SFFV, which showed lower levels. Nb11 in vivo expression was evaluated in C57BL/6 mice after intravenous administration of AAV8 vectors. Nb11 serum levels increased steadily along time, reaching 1-3 microgram/mL two months post-treatment with the vector having the CAG promoter (AAV-CAG-Nb11), without evidence of toxicity. To test the antitumor potential of this vector, mice that received AAV-CAG-Nb11, or saline as control, were challenged with colon adenocarcinoma cells (MC38). AAV-CAG-Nb11 treatment prevented tumor formation in 30% of mice, significantly increasing survival. These data suggest that continuous expression of immunomodulatory nanobodies from long-term expression vectors could have antitumor effects with low toxicity.

Indexed as

AAV vectorcancergene therapyimmunotherapynanobodyPD-1PD-L1VHH

Identifiers

PMID33276580
PMCPMC7761623

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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.