Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 01 2020
31 01 2020
Historique:
received:
28
06
2019
accepted:
03
10
2019
entrez:
2
2
2020
pubmed:
2
2
2020
medline:
12
5
2020
Statut:
epublish
Résumé
Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported by NKTR-214 increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increases the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a phase 1 trial. In conclusion, NKTR-214 may have the potential to improve the antitumor activity of ACT in humans through increased in vivo expansion and polyfunctionality of the adoptively transferred T cells.
Identifiants
pubmed: 32005809
doi: 10.1038/s41467-019-12901-3
pii: 10.1038/s41467-019-12901-3
pmc: PMC6994533
doi:
Substances chimiques
Interleukin-2
0
Receptors, Interleukin-2
0
Polyethylene Glycols
3WJQ0SDW1A
bempegaldesleukin
BNO1JG5MZC
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
660Subventions
Organisme : NCI NIH HHS
ID : P01 CA244118
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197633
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009120
Pays : United States
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