A novel format for recombinant antibody-interleukin-2 fusion proteins exhibits superior tumor-targeting properties
fibronectin
immunocytokines
interleukin-2
protein engineering
tumor targeting
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
13 Oct 2020
13 Oct 2020
Historique:
received:
11
06
2020
accepted:
17
08
2020
entrez:
28
10
2020
pubmed:
29
10
2020
medline:
29
10
2020
Statut:
epublish
Résumé
The targeted delivery of interleukin-2 to the tumor is gaining attention as an avenue to potentiate the action of T and NK cells at the site of disease. We have previously described the fusion of the L19 antibody, specific to the EDB domain of fibronectin, with human interleukin-2, using a non-covalent homodimeric diabody format. Here, we describe four novel formats for the L19-IL2 fusion, featuring different arrangements of antibody and IL2. A comparative quantitative biodistribution analysis in tumor-bearing mice using radioiodinated proteins revealed that the novel format (L19L19-IL2, with the antibody in single-chain diabody format) exhibited the best biodistribution results.
Identifiants
pubmed: 33110477
doi: 10.18632/oncotarget.27726
pii: 27726
pmc: PMC7566808
doi:
Types de publication
Journal Article
Langues
eng
Pagination
3698-3711Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST Prof. Dr. Dario Neri is co-founder and shareholder of Philogen, a biotech company having exclusive rights on the L19 antibody. Mr. Tiziano Ongaro, Mr. Baptiste Gouyou, Mr. Riccardo Corbellari and Dr. Alessandra Villa are employees of Philochem AG, a daughter company of Philogen. Mr. Marco Stringhini is a student at ETH Zurich. The authors have no additional financial interests to disclose. A patent covering L19L19-IL2 has been filed [WO/2020/070150].
Références
J Immunol. 2014 Jun 15;192(12):5451-8
pubmed: 24907378
Clin Cancer Res. 2016 Feb 1;22(3):680-90
pubmed: 26832745
Int J Cancer. 2020 May 1;146(9):2518-2530
pubmed: 31374124
Expert Rev Clin Immunol. 2014 Feb;10(2):207-17
pubmed: 24410537
J Nucl Med. 2006 Jul;47(7):1127-35
pubmed: 16818947
Cancer Immunol Res. 2019 Apr;7(4):572-583
pubmed: 30782667
Cancer Immunol Immunother. 2019 Sep;68(9):1547-1559
pubmed: 31482307
Ann Surg Oncol. 2005 Dec;12(12):1005-16
pubmed: 16283570
Invest New Drugs. 1993 May-Aug;11(2-3):211-7
pubmed: 8262734
EMBO J. 1987 Aug;6(8):2337-42
pubmed: 2822387
Immunity. 2017 Apr 18;46(4):577-586
pubmed: 28410988
Clin Cancer Res. 2012 Apr 1;18(7):2039-47
pubmed: 22271879
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6444-8
pubmed: 8341653
Cancer Discov. 2019 Jun;9(6):711-721
pubmed: 30988166
Sci Transl Med. 2016 Nov 30;8(367):367ra166
pubmed: 27903862
J Urol. 2010 Dec;184(6):2540-8
pubmed: 21030045
Blood. 1999 Jul 1;94(1):192-8
pubmed: 10381513
N Engl J Med. 2012 Jun 28;366(26):2455-65
pubmed: 22658128
Cancer Immunol Res. 2013 Aug;1(2):134-43
pubmed: 24777501
Nat Commun. 2020 Jan 31;11(1):661
pubmed: 32005826
Protein Eng Des Sel. 2013 Oct;26(10):561-9
pubmed: 24025193
N Engl J Med. 2011 Dec 1;365(22):2067-77
pubmed: 22129253
Nature. 2019 Jan;565(7738):186-191
pubmed: 30626941
Clin Cancer Res. 2011 Dec 15;17(24):7732-42
pubmed: 22028492
J Invest Dermatol. 2013 Mar;133(3):751-758
pubmed: 23096716
Lancet. 2014 Sep 20;384(9948):1109-17
pubmed: 25034862
Blood. 2002 Mar 1;99(5):1659-65
pubmed: 11861281
N Engl J Med. 2012 Jun 28;366(26):2443-54
pubmed: 22658127
Cancer Discov. 2018 Sep;8(9):1069-1086
pubmed: 30115704
Eur J Cancer. 2010 Nov;46(16):2926-35
pubmed: 20797845
J Biol Chem. 1998 Aug 21;273(34):21769-76
pubmed: 9705314
Nat Rev Immunol. 2015 May;15(5):283-94
pubmed: 25882245
Br J Cancer. 1993 Feb;67(2):304-10
pubmed: 8431359
Cancer. 2008 Jul 15;113(2):293-301
pubmed: 18457330
Anticancer Drugs. 2020 Sep;31(8):799-805
pubmed: 32304410
Clin Cancer Res. 2008 Oct 15;14(20):6515-24
pubmed: 18927291
Sci Transl Med. 2012 Jun 6;4(137):137ra74
pubmed: 22674552
Cancer Immunol Immunother. 2014 Sep;63(9):901-10
pubmed: 24893857
J Cell Biol. 1989 Mar;108(3):1139-48
pubmed: 2646306
Int J Cancer. 1994 Dec 1;59(5):612-8
pubmed: 7525495
Cancer Immunol Immunother. 2012 Dec;61(12):2261-71
pubmed: 22678096
Cancer Discov. 2020 Aug;10(8):1158-1173
pubmed: 32439653
Clin Cancer Res. 2019 Jan 15;25(2):698-709
pubmed: 30327303
N Engl J Med. 2011 Dec 1;365(22):2055-66
pubmed: 22129252
Radiother Oncol. 2015 Sep;116(3):438-42
pubmed: 26138057
J Pharm Sci. 2008 Jun;97(6):2041-4
pubmed: 17847072
Nat Med. 2016 Sep;22(9):991-3
pubmed: 27500725
Oncoimmunology. 2017 Jan 11;6(3):e1277306
pubmed: 28405498
Cancer Res. 1999 Jan 15;59(2):347-52
pubmed: 9927045
Blood. 2009 Mar 5;113(10):2275-83
pubmed: 19005180
J Nucl Med. 2012 Jun;53(6):922-7
pubmed: 22577235