Search: id:"swepub:oai:lup.lub.lu.se:0f3a3908-b3cb-40b4-89fd-c6d7872c43e0" >
ATOR-1017 (evunzeki...
-
Enell Smith, KarinAlligator Biosciences AB
(author)
ATOR-1017 (evunzekibart), an Fc-gamma receptor conditional 4-1BB agonist designed for optimal safety and efficacy, activates exhausted T cells in combination with anti-PD-1
- Article/chapterEnglish2023
Publisher, publication year, extent ...
Numbers
-
LIBRIS-ID:oai:lup.lub.lu.se:0f3a3908-b3cb-40b4-89fd-c6d7872c43e0
-
https://lup.lub.lu.se/record/0f3a3908-b3cb-40b4-89fd-c6d7872c43e0URI
-
https://doi.org/10.1007/s00262-023-03548-7DOI
Supplementary language notes
-
Language:English
-
Summary in:English
Part of subdatabase
Classification
-
Subject category:art swepub-publicationtype
-
Subject category:ref swepub-contenttype
Notes
-
Background: 4-1BB (CD137) is a co-stimulatory receptor highly expressed on tumor reactive effector T cells and NK cells, which upon stimulation prolongs persistence of tumor reactive effector T and NK cells within the tumor and induces long-lived memory T cells. 4-1BB agonistic antibodies have been shown to induce strong anti-tumor effects that synergize with immune checkpoint inhibitors. The first generation of 4-1BB agonists was, however, hampered by dose-limiting toxicities resulting in suboptimal dose levels or poor agonistic activity. Methods: ATOR-1017 (evunzekibart), a second-generation Fc-gamma receptor conditional 4-1BB agonist in IgG4 format, was designed to overcome the limitations of the first generation of 4-1BB agonists, providing strong agonistic effect while minimizing systemic immune activation and risk of hepatoxicity. The epitope of ATOR-1017 was determined by X-ray crystallography, and the functional activity was assessed in vitro and in vivo as monotherapy or in combination with anti-PD1. Results: ATOR-1017 binds to a unique epitope on 4-1BB enabling ATOR-1017 to activate T cells, including cells with an exhausted phenotype, and NK cells, in a cross-linking dependent, FcγR-conditional, manner. This translated into a tumor-directed and potent anti-tumor therapeutic effect in vivo, which was further enhanced with anti-PD-1 treatment. Conclusions: These preclinical data demonstrate a strong safety profile of ATOR-1017, together with its potent therapeutic effect as monotherapy and in combination with anti-PD1, supporting further clinical development of ATOR-1017.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
-
Fritzell, SaraAlligator Biosciences AB
(author)
-
Nilsson, AnneliAlligator Biosciences AB
(author)
-
Barchan, Karin
(author)
-
Rosén, Anna
(author)
-
Schultz, Lena
(author)
-
Varas, LauraAlligator Biosciences AB
(author)
-
Säll, AnnaAlligator Biosciences AB
(author)
-
Rose, Nadia
(author)
-
Håkansson, MariaSARomics Biostructures AB
(author)
-
von Schantz, LauraAlligator Biosciences AB(Swepub:lu)med-lmt
(author)
-
Ellmark, PeterLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Alligator Biosciences AB(Swepub:lu)immt-pel
(author)
-
Alligator Biosciences ABSARomics Biostructures AB
(creator_code:org_t)
Related titles
-
In:Cancer Immunology, Immunotherapy72:12, s. 4145-41590340-7004
Internet link
Find in a library
To the university's database
- By the author/editor
-
Enell Smith, Kar ...
-
Fritzell, Sara
-
Nilsson, Anneli
-
Barchan, Karin
-
Rosén, Anna
-
Schultz, Lena
-
show more...
-
Varas, Laura
-
Säll, Anna
-
Rose, Nadia
-
Håkansson, Maria
-
von Schantz, Lau ...
-
Ellmark, Peter
-
show less...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
-
MEDICAL AND HEAL ...
-
and Clinical Medicin ...
-
and Cancer and Oncol ...
- Articles in the publication
-
Cancer Immunolog ...
- By the university
-
Lund University