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ATOR-1017 (evunzeki...
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Enell Smith, KarinAlligator Biosciences AB
(författare)
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
- Artikel/kapitelEngelska2023
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:0f3a3908-b3cb-40b4-89fd-c6d7872c43e0
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https://lup.lub.lu.se/record/0f3a3908-b3cb-40b4-89fd-c6d7872c43e0URI
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https://doi.org/10.1007/s00262-023-03548-7DOI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Fritzell, SaraAlligator Biosciences AB
(författare)
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Nilsson, AnneliAlligator Biosciences AB
(författare)
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Barchan, Karin
(författare)
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Rosén, Anna
(författare)
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Schultz, Lena
(författare)
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Varas, LauraAlligator Biosciences AB
(författare)
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Säll, AnnaAlligator Biosciences AB
(författare)
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Rose, Nadia
(författare)
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Håkansson, MariaSARomics Biostructures AB
(författare)
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von Schantz, LauraAlligator Biosciences AB(Swepub:lu)med-lmt
(författare)
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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
(författare)
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Alligator Biosciences ABSARomics Biostructures AB
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cancer Immunology, Immunotherapy72:12, s. 4145-41590340-7004
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Till lärosätets databas
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Enell Smith, Kar ...
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Fritzell, Sara
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Nilsson, Anneli
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Barchan, Karin
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Rosén, Anna
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Schultz, Lena
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visa fler...
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Varas, Laura
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Säll, Anna
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Rose, Nadia
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Håkansson, Maria
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von Schantz, Lau ...
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Ellmark, Peter
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Cancer Immunolog ...
- Av lärosätet
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Lunds universitet