Targeting an engineered cytokine with interleukin-2 and interleukin-15 activity to the neovasculature of solid tumors.
EDB of fibronectin
antibody-cytokine fusion proteins
engineered cytokine
immunocytokines
immunotherapy
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
03 Nov 2020
03 Nov 2020
Historique:
received:
30
07
2020
accepted:
24
09
2020
entrez:
20
11
2020
pubmed:
21
11
2020
medline:
21
11
2020
Statut:
epublish
Résumé
There is a growing interest in the antibody-based delivery of cytokines to the tumor environment as a means to boost the anti-cancer activity of tumor-resident T cells and NK cells. Here, we describe the expression and characterization of fusion proteins, featuring the L19 antibody (specific to the alternatively-spliced EDB domain of fibronectin) and an engineered cytokine with interleukin-2 and interleukin-15 properties. The cytokine moiety was fused either at the N-terminal or at the C-terminal extremity and both fusion proteins showed a selective tumor accumulation in a quantitative biodistribution experiment. The N-terminal fusion inhibited tumor growth in immunocompetent mice bearing F9 carcinomas or WEHI-164 sarcomas when used as single agent. The anticancer activity was compared to the one of the same cytokine payload used as recombinant protein or fused to an anti-hen egg lysozyme antibody, serving as negative control of irrelevant specificity in the mouse. These results indicate that the antibody-based delivery of engineered cytokines to the tumor neovasculature may mediate a potent anticancer activity.
Identifiants
pubmed: 33216834
doi: 10.18632/oncotarget.27772
pii: 27772
pmc: PMC7646832
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3972-3983Informations de copyright
Copyright: © 2020 Mortensen et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST D.N. is a cofounder, shareholder and board member at Philogen. The other authors declare no competing interests.
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