ICOS agonism by JTX-2011 (vopratelimab) requires initial T cell priming and Fc cross-linking for optimal T cell activation and anti-tumor immunity in preclinical models

  1. Hanson, Amanda
  2. Elpek, Kutlu
  3. Duong, Ellen
  4. Shallberg, Lindsey
  5. Fan, Martin
  6. Johnson, Calvin
  7. Wallace, Matthew
  8. Mabry, George R.
  9. Sazinsky, Stephen
  10. Pepper, Lauren
  11. Shu, Chengyi J.
  12. Sathyanarayanan, Sriram
  13. Zuerndorfer, Sarah
  14. Simpson, Tyler
  15. Gostissa, Monica
  16. Briskin, Michael
  17. Law, Deborah
  18. Michaelson, Jennifer
  19. Harvey, Christopher ORCID logo

Download
file.pdf 2,14MB
WeightNameValue
1000 Titel
  • ICOS agonism by JTX-2011 (vopratelimab) requires initial T cell priming and Fc cross-linking for optimal T cell activation and anti-tumor immunity in preclinical models
1000 Autor/in
  1. Hanson, Amanda |
  2. Elpek, Kutlu |
  3. Duong, Ellen |
  4. Shallberg, Lindsey |
  5. Fan, Martin |
  6. Johnson, Calvin |
  7. Wallace, Matthew |
  8. Mabry, George R. |
  9. Sazinsky, Stephen |
  10. Pepper, Lauren |
  11. Shu, Chengyi J. |
  12. Sathyanarayanan, Sriram |
  13. Zuerndorfer, Sarah |
  14. Simpson, Tyler |
  15. Gostissa, Monica |
  16. Briskin, Michael |
  17. Law, Deborah |
  18. Michaelson, Jennifer |
  19. Harvey, Christopher |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-09-24
1000 Erschienen in
1000 Quellenangabe
  • 15(9):e0239595
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1371/journal.pone.0239595 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514066/ |
1000 Ergänzendes Material
  • https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239595#sec017 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Immunotherapy checkpoint inhibitors, such as antibodies targeting PD-1 and CTLA-4, have demonstrated the potential of harnessing the immune system to treat cancer. However, despite encouraging results particularly with respect to survival, only a minority of patients benefit from these therapies. In clinical studies aimed at understanding changes in the immune system following immunotherapy treatment, ICOS (Inducible T cell CO-Stimulator) was shown to be significantly up-regulated on CD4+ T cells and this was associated with clinical activity, indicating that ICOS stimulatory activity may be beneficial in the treatment of solid tumors. In this report, we describe the generation of specific, species cross-reactive, agonist antibodies to ICOS, including the humanized clinical candidate, JTX-2011 (vopratelimab). Preclinical studies suggest that the ICOS stimulating antibodies require Fc receptor cross-linking for optimal agonistic activity. Notably, the ICOS antibodies do not exhibit superagonist properties but rather require T cell receptor (TCR)-mediated upregulation of ICOS for agonist activity. Treatment with the ICOS antibodies results in robust anti-tumor benefit and long-term protection in preclinical syngeneic mouse tumor models. Additional benefit is observed when the ICOS antibodies are administered in combination with anti-PD-1 and anti-CTLA-4 therapies. Based on the preclinical data, JTX-2011 is currently being developed in the clinical setting for the treatment of solid tumors.
1000 Sacherschließung
lokal Cancer and neoplasms
lokal Cloning
lokal Cancer immunotherapy
lokal Antibody therapy
lokal Flow cytometry
lokal T cells
lokal Cancer treatment
lokal Antibodies
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/SGFuc29uLCBBbWFuZGE=|https://frl.publisso.de/adhoc/uri/RWxwZWssIEt1dGx1|https://frl.publisso.de/adhoc/uri/RHVvbmcsIEVsbGVu|https://frl.publisso.de/adhoc/uri/U2hhbGxiZXJnLCBMaW5kc2V5|https://frl.publisso.de/adhoc/uri/RmFuLCBNYXJ0aW4=|https://frl.publisso.de/adhoc/uri/Sm9obnNvbiwgQ2Fsdmlu|https://frl.publisso.de/adhoc/uri/V2FsbGFjZSwgTWF0dGhldw==|https://frl.publisso.de/adhoc/uri/TWFicnksIEdlb3JnZSBSLg==|https://frl.publisso.de/adhoc/uri/U2F6aW5za3ksIFN0ZXBoZW4=|https://frl.publisso.de/adhoc/uri/UGVwcGVyLCBMYXVyZW4=|https://frl.publisso.de/adhoc/uri/U2h1LCBDaGVuZ3lpIEou|https://frl.publisso.de/adhoc/uri/U2F0aHlhbmFyYXlhbmFuLCBTcmlyYW0=|https://frl.publisso.de/adhoc/uri/WnVlcm5kb3JmZXIsIFNhcmFo|https://frl.publisso.de/adhoc/uri/U2ltcHNvbiwgVHlsZXI=|https://frl.publisso.de/adhoc/uri/R29zdGlzc2EsIE1vbmljYQ==|https://frl.publisso.de/adhoc/uri/QnJpc2tpbiwgTWljaGFlbA==|https://frl.publisso.de/adhoc/uri/TGF3LCBEZWJvcmFo|https://frl.publisso.de/adhoc/uri/TWljaGFlbHNvbiwgSmVubmlmZXI=|http://orcid.org/0000-0001-6103-1909
1000 (Academic) Editor
1000 Label
1000 Förderer
  1. Jounce Therapeutics |
1000 Fördernummer
  1. -
1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Jounce Therapeutics |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6453055.rdf
1000 Erstellt am 2023-07-07T09:35:48.593+0200
1000 Erstellt von 337
1000 beschreibt frl:6453055
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Thu Aug 03 13:31:06 CEST 2023
1000 Objekt bearb. Thu Aug 03 13:30:51 CEST 2023
1000 Vgl. frl:6453055
1000 Oai Id
  1. oai:frl.publisso.de:frl:6453055 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source