Evidence map›Paper›PMID 37949616›Full record

ArticleJournal for immunotherapy of cancer2023

Local and distant response to intratumoral immunotherapy assessed by immunoPET in mice.

Louis Meyblum, Céline Chevaleyre, Sandrine Susini, Benoit Jego, Frederic Deschamps, Dimitri Kereselidze, Baptiste Bonnet, Aurelien Marabelle, Thierry de Baere, Vincent Lebon and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

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  8. Non-specific irreversibleEJNMMI research · 2024
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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

12 authors at 2 institutions in 1 country.

Louis Meyblum *Université Paris-Saclay, CEA, CNRS, INSERM UMR1281, Laboratoire d'Imagerie Biomédicale Multimodale Paris Saclay (BioMaps), Orsay, France.
Céline Chevaleyre *Université Paris-Saclay, CEA, CNRS, INSERM UMR1281, Laboratoire d'Imagerie Biomédicale Multimodale Paris Saclay (BioMaps), Orsay, France.
Sandrine SusiniLaboratoire de Recherche Translationnelle en Immunothérapie (LRTI), INSERM U1015, Villejuif, France.
Benoit JegoUniversité Paris-Saclay, CEA, CNRS, INSERM UMR1281, Laboratoire d'Imagerie Biomédicale Multimodale Paris Saclay (BioMaps), Orsay, France.
Frederic DeschampsDépartement d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.
Dimitri KereselidzeUniversité Paris-Saclay, CEA, CNRS, INSERM UMR1281, Laboratoire d'Imagerie Biomédicale Multimodale Paris Saclay (BioMaps), Orsay, France.
Baptiste BonnetDépartement d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.
Aurelien MarabelleLaboratoire de Recherche Translationnelle en Immunothérapie (LRTI), INSERM U1015, Villejuif, France.ORCID 0000-0002-5816-3019
Thierry de BaereDépartement d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.
Vincent LebonUniversité Paris-Saclay, CEA, CNRS, INSERM UMR1281, Laboratoire d'Imagerie Biomédicale Multimodale Paris Saclay (BioMaps), Orsay, France.
Lambros TselikasDépartement d'Anesthésie, Chirurgie et Interventionnel (DACI), Service de Radiologie Interventionnelle, Gustave Roussy, Villejuif, France.ORCID 0000-0002-8878-4916
Charles TruilletUniversité Paris-Saclay, CEA, CNRS, INSERM UMR1281, Laboratoire d'Imagerie Biomédicale Multimodale Paris Saclay (BioMaps), Orsay, France charles.truillet@universite-paris-saclay.fr.ORCID 0000-0002-1782-5418
Centre National de la Recherche Scientifique · FRInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite the promising efficacy of immune checkpoint blockers (ICB), tumor resistance and immune-related adverse events hinder their success in cancer treatment. To address these challenges, intratumoral delivery of immunotherapies has emerged as a potential solution, aiming to mitigate side effects through reduced systemic exposure while increasing effectiveness by enhancing local bioavailability. However, a comprehensive understanding of the local and systemic distribution of ICBs following intratumoral administration, as well as their impact on distant tumors, remains crucial for optimizing their therapeutic potential.To comprehensively investigate the distribution patterns following the intratumoral and intravenous administration of radiolabeled anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and to assess its corresponding efficacy in both injected and non-injected tumors, we conducted an immunoPET imaging study.

methodsCT26 and MC38 syngeneic colorectal tumor cells were implanted subcutaneously on both flanks of Balb/c and C57Bl/6 mice, respectively. Hamster anti-mouse CTLA-4 antibody (9H10) labeled with zirconium-89 ([

resultsHalf of the dose was cleared into the blood 1 hour after intratumoral administration. Despite this, 7 days post-injection, 6-8% of the dose remained in the intratumoral-injected tumors. CT26 tumors with prolonged ICB exposure demonstrated complete responses. Seven days post-injection, the contralateral non-injected tumor uptake of the ICB was comparable to the one achieved through intravenous administration (7.5±1.7% ID.cm

conclusionsImmunoPET-derived pharmacokinetics supports intratumoral injection of ICBs to decrease systemic exposure while maintaining efficacy compared with intravenous. Intratumoral-ICBs lead to high local drug exposure while maintaining significant therapeutic exposure in non-injected tumors. This immunoPET approach is applicable for clinical practice to support evidence-based drug development.

Indexed as

Colorectal NeoplasmsImmunotherapyAnimalsCD8-Positive T-LymphocytesCTLA-4 AntigenMiceTumor MicroenvironmentCTLA-4 AntigenCTLA-4 AntigenDrug Evaluation, PreclinicalImmune Checkpoint InhibitorsTumor Biomarkers

Identifiers

PMID37949616
PMCPMC10649793
OpenAlexW4388564351

What OpenQuestion holds

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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.