دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity.
المؤلفون: Rubio-Pérez L; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), 28041 Madrid, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.; Chair for Immunology UFV/Merck, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, 28223 Madrid, Spain., Frago S; Department of Antibody Engineering, Leadartis SL, QUBE Technology Park, Tres Cantos, 28760 Madrid, Spain., Compte M; Department of Antibody Engineering, Leadartis SL, QUBE Technology Park, Tres Cantos, 28760 Madrid, Spain., Navarro R; Department of Antibody Engineering, Leadartis SL, QUBE Technology Park, Tres Cantos, 28760 Madrid, Spain., Harwood SL; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark., Lázaro-Gorines R; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), 28041 Madrid, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain., Gómez-Rosel M; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), 28041 Madrid, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain., Hangiu O; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), 28041 Madrid, Spain.; Department of Antibody Engineering, Leadartis SL, QUBE Technology Park, Tres Cantos, 28760 Madrid, Spain., Silva-Pilipich N; Division of DNA and RNA Medicine, Cima Universidad de Navarra, 31008 Pamplona, Spain.; Instituto de Investigación Sanitaria de Navarra (IdISNA) and CCUN, 31008 Pamplona, Spain., Vanrell L; Facultad de Ingeniería, Universidad ORT Uruguay, 11100 Montevideo, Uruguay.; Nanogrow Biotech, Montevideo 11500, Uruguay., Smerdou C; Division of DNA and RNA Medicine, Cima Universidad de Navarra, 31008 Pamplona, Spain.; Instituto de Investigación Sanitaria de Navarra (IdISNA) and CCUN, 31008 Pamplona, Spain., Álvarez-Vallina L; Cancer Immunotherapy Unit (UNICA), Department of Immunology, Hospital Universitario12 de Octubre (H12O), 28041 Madrid, Spain.; Immuno-Oncology and Immunotherapy Group, Instituto de Investigación Sanitaria 12 de Octubre (imas12), 28041 Madrid, Spain.; H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.; Chair for Immunology UFV/Merck, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, 28223 Madrid, Spain.
المصدر: Antibodies (Basel, Switzerland) [Antibodies (Basel)] 2024 Apr 24; Vol. 13 (2). Date of Electronic Publication: 2024 Apr 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101587489 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4468 (Electronic) Linking ISSN: 20734468 NLM ISO Abbreviation: Antibodies (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, 2012-
مستخلص: 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.
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معلومات مُعتمدة: PID2020-117323RB-100 and PDC2021-121711-100 Ministerio de Ciencia e Innovación; DTS20/00089 and PI20/00415 Instituto de Salud Carlos III; PROYE19084ALVA and PRYGN234844ALVA Asociación Española Contra el Cáncer
فهرسة مساهمة: Keywords: 4-1BB costimulation; cancer immunotherapy; epithelial growth factor receptor; immune checkpoint blockade; trispecific antibody
تواريخ الأحداث: Date Created: 20240528 Latest Revision: 20240530
رمز التحديث: 20240530
مُعرف محوري في PubMed: PMC11130918
DOI: 10.3390/antib13020034
PMID: 38804302
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4468
DOI:10.3390/antib13020034