Generation and
antibodies, neoplasm
antigens
cytokines
immunotherapy
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
accepted:
30
08
2022
entrez:
14
9
2022
pubmed:
15
9
2022
medline:
17
9
2022
Statut:
ppublish
Résumé
In this study, we describe the generation of a fully human monoclonal antibody (named '7NP2') targeting human fibroblast activation protein (FAP), an antigen expressed in the microenvironment of different types of solid neoplasms. 7NP2 was isolated from a synthetic antibody phage display library and was improved by one round of mutagenesis-based affinity maturation. The tumor recognition properties of the antibody were validated by immunofluorescence procedures performed on cancer biopsies from human patients. A fusion protein consisting of the 7NP2 antibody linked to interleukin (IL)-12 was generated and the anticancer activity of the murine surrogate product (named mIL12-7NP2) was evaluated in mouse models. Furthermore, the safety of the fully human product (named IL12-7NP2) was evaluated in Biodistribution analysis in tumor-bearing mice confirmed the ability of the product to selectively localize to solid tumors while sparing healthy organs. Encouraged by these results, therapy studies were conducted The results obtained in this work provided a rationale for future clinical translation activities using IL12-7NP2.
Sections du résumé
BACKGROUND
In this study, we describe the generation of a fully human monoclonal antibody (named '7NP2') targeting human fibroblast activation protein (FAP), an antigen expressed in the microenvironment of different types of solid neoplasms.
METHODS
7NP2 was isolated from a synthetic antibody phage display library and was improved by one round of mutagenesis-based affinity maturation. The tumor recognition properties of the antibody were validated by immunofluorescence procedures performed on cancer biopsies from human patients. A fusion protein consisting of the 7NP2 antibody linked to interleukin (IL)-12 was generated and the anticancer activity of the murine surrogate product (named mIL12-7NP2) was evaluated in mouse models. Furthermore, the safety of the fully human product (named IL12-7NP2) was evaluated in
RESULTS
Biodistribution analysis in tumor-bearing mice confirmed the ability of the product to selectively localize to solid tumors while sparing healthy organs. Encouraged by these results, therapy studies were conducted
CONCLUSIONS
The results obtained in this work provided a rationale for future clinical translation activities using IL12-7NP2.
Identifiants
pubmed: 36104101
pii: jitc-2022-005282
doi: 10.1136/jitc-2022-005282
pmc: PMC9476130
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Interleukin-12
187348-17-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: DN is a co-founder and shareholder of Philogen (www.philogen.com), a Swiss- Italian Biotech company that operates in the field of ligand-based pharmacodelivery. LN, FP, AE, NF, EPuc, CDN, EPro, RC, MM, and RD are employees of Philochem AG, daughter company of Philogen acting as discovery unit of the group.
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