Evidence map›Paper›PMID 38804302›Full record

ArticleAntibodies (Basel, Switzerland)2024

Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.

Laura Rubio-Pérez, Susana Frago, Marta Compte, Rocío Navarro, Seandean L Harwood, Rodrigo Lázaro-Gorines, Marina Gómez-Rosel, Oana Hangiu, Noelia Silva-Pilipich, Lucía Vanrell and 2 more

Abstract read
In one paragraph

Article in Antibodies (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
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.

Laura Rubio-PérezCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.ORCID 0000-0002-2877-6092
Susana FragoDepartment of Antibody Engineering, Leadartis SL, QUBE Technology Park, Tres Cantos, 28760 Madrid, Spain.
Marta CompteDepartment of Antibody Engineering, Leadartis SL, QUBE Technology Park, Tres Cantos, 28760 Madrid, Spain.ORCID 0000-0002-7138-9266
Rocío NavarroDepartment of Antibody Engineering, Leadartis SL, QUBE Technology Park, Tres Cantos, 28760 Madrid, Spain.
Seandean L HarwoodDepartment of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark.
Rodrigo Lázaro-GorinesCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.
Marina Gómez-RoselCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.
Oana HangiuCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.
Noelia Silva-PilipichDivision of DNA and RNA Medicine, Cima Universidad de Navarra, 31008 Pamplona, Spain.ORCID 0000-0003-2928-9226
Lucía VanrellFacultad de Ingeniería, Universidad ORT Uruguay, 11100 Montevideo, Uruguay.
Cristian SmerdouDivision of DNA and RNA Medicine, Cima Universidad de Navarra, 31008 Pamplona, Spain.ORCID 0000-0002-6861-6579
Luis Álvarez-VallinaCancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.ORCID 0000-0003-3053-6757

Funding

Asociación Española Contra el Cáncer PROYE19084ALVA and PRYGN234844ALVAInstituto de Salud Carlos III DTS20/00089 and PI20/00415Ministerio de Ciencia e Innovación PID2020-117323RB-100 and PDC2021-121711-100
6 · The paper itself

Abstract

Immune checkpoint blockade has changed the treatment paradigm for advanced solid tumors, but the overall response rates are still limited. The combination of checkpoint blockade with anti-4-1BB antibodies to stimulate tumor-infiltrating T cells has shown anti-tumor activity in human trials. However, the further clinical development of these antibodies has been hampered by significant off-tumor toxicities. Here, we generated an anti-4-1BB/EGFR/PD-L1 trispecific antibody consisting of a triple-targeting tandem trimerbody (TT) fused to an engineered silent Fc region. This antibody (IgTT-4E1-S) was designed to combine the blockade of the PD-L1/PD-1 axis with conditional 4-1BB costimulation specifically confined to the tumor microenvironment (TME). The antibody demonstrated simultaneous binding to purified EGFR, PD-L1, and 4-1BB in solution, effective blockade of the PD-L1/PD1 interaction, and potent 4-1BB-mediated costimulation, but only in the presence of EGFR-expressing cells. These results demonstrate the feasibility of IgTT-4E1-S specifically blocking the PD-L1/PD-1 axis and inducing EGFR-conditional 4-1BB agonist activity.

Indexed as

4-1BB costimulationcancer immunotherapyepithelial growth factor receptorimmune checkpoint blockadetrispecific antibody

Identifiers

PMID38804302
PMCPMC11130918

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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.