Evidence map›Paper›PMID 35141398›Full record

ArticleMolecular therapy oncolytics2022

Highly efficient PD-1-targeted CRISPR-Cas9 for tumor-infiltrating lymphocyte-based adoptive T cell therapy.

Christopher Aled Chamberlain, Eric Paul Bennett, Anders Handrup Kverneland, Inge Marie Svane, Marco Donia, Özcan Met

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Molecular therapy oncolytics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06783270 (T-cell Therapy with CRISPR PD1-edited Tumor Infiltrating Lymphocytes for Patients with Metastatic Melanoma), which is not on this map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
6.6field-weighted citation impact, top 2% 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.

NCT06783270 phase1recruitingnot on this mapstarted 2024, after this paper: background citation

T-cell Therapy with CRISPR PD1-edited Tumor Infiltrating Lymphocytes for Patients with Metastatic Melanoma

TypeinterventionalSponsorInge Marie SvaneRan2024 to 2028Enrolled10ConditionsMelanoma MetastaticArmsTIL therapy
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
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  3. Adoptive cell therapies in thoracic malignancies: a comprehensive review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  4. Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026
    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

6 authors at 2 institutions in 1 country.

Christopher Aled ChamberlainNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 25C, 2730 Herlev, Denmark.
Eric Paul BennettDepartment of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Nørre Allé 20, 2200 Copenhagen N, Denmark.
Anders Handrup KvernelandNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 25C, 2730 Herlev, Denmark.
Inge Marie SvaneNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 25C, 2730 Herlev, Denmark.
Marco DoniaNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 25C, 2730 Herlev, Denmark.
Özcan MetNational Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Borgmester Ib Juuls Vej 25C, 2730 Herlev, Denmark.
Copenhagen University Hospital · DKUniversity of Copenhagen · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adoptive T cell therapy (ACT) with expanded tumor-infiltrating lymphocytes (TIL) can induce durable responses in cancer patients from multiple histologies, with response rates of up to 50%. Antibodies blocking the engagement of the inhibitory receptor programmed cell death protein 1 (PD-1) have been successful across a variety of cancer diagnoses. We hypothesized that these approaches could be combined by using CRISPR-Cas9 gene editing to knock out PD-1 in TILs from metastatic melanoma and head-and-neck, thyroid, and colorectal cancer. Non-viral, non-plasmid-based PD-1 knockout was carried out immediately prior to the traditional 14-day TIL-based ACT rapid-expansion protocol. A median 87.53% reduction in cell surface PD-1 expression was observed post-expansion and confirmed at the genomic level. No off-target editing was detected, and PD-1 knockout had no effect on final fold expansion. Edited cells exhibited few phenotypic differences and matched control functionality. Pre-clinical-scale results were confirmed at a clinical scale by generating a PD-1-deficient TIL product using the good manufacturing practice facilities, equipment, procedures, and starting material used for standard patient treatment. Our results demonstrate that simple, non-viral, non-plasmid-based CRISPR-Cas9 methods can be feasibly adopted into a TIL-based ACT protocol to produce treatment products deficient in molecules such as PD-1, without any evident negative effects.

Indexed as

adoptive cell therapyCRISPR-Cas9gene editingimmunotherapyPD-1TIL therapytumor-infiltrating lymphocytes

Identifiers

PMID35141398
PMCPMC8807971
OpenAlexW4205307302

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.