Antibody-based tumor vascular theranostics targeting endosialin/TEM1 in a new mouse tumor vascular model.

Détails

ID Serval
serval:BIB_7667F1778B28
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Antibody-based tumor vascular theranostics targeting endosialin/TEM1 in a new mouse tumor vascular model.
Périodique
Cancer Biology and Therapy
Auteur(s)
Li C., Chacko A.M., Hu J., Hasegawa K., Swails J., Grasso L., El-Deiry W.S., Nicolaides N., Muzykantov V.R., Divgi C.R., Coukos G.
ISSN
1555-8576 (Electronic)
ISSN-L
1538-4047
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
15
Numéro
4
Pages
443-451
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.Publication Status: ppublish
Résumé
Tumor endothelial marker 1 (TEM1, endosialin) is a tumor vascular marker with significant diagnostic and therapeutic potential. However, in vivo small animal models to test affinity reagents specifically targeted to human (h)TEM1 are limited. We describe a new mouse tumor model where tumor vascular endothelial cells express hTEM1 protein.
METHODS: Immortalized murine endothelial cells MS1 were engineered to express hTEM1 and firefly luciferase and were inoculated in nude mice either alone, to form hemangioma-like endothelial grafts, or admixed with ID8 ovarian tumor cells, to form chimeric endothelial-tumor cell grafts. MORAb-004, a monoclonal humanized IgG 1 antibody specifically recognizing human TEM1 was evaluated for targeted theranostic applications, i.e., for its ability to affect vascular grafts expressing hTEM1 as well as being a tool for molecular positron emission tomography (PET) imaging.
RESULTS: Naked MORAb-004 treatment of mice bearing angioma grafts or chimeric endothelial-tumor grafts significantly suppressed the ability of hTEM1-positive endothelial cells, but not control endothelial cells, to form grafts and dramatically suppressed local angiogenesis. In addition, highly efficient radioiodination of MORAb-004 did not impair its affinity for hTEM1, and [ (124)I]-MORAb-004-PET enabled non-invasive visualization of tumors enriched with hTEM1-positive, but not hTEM1 negative vasculature with high degree of specificity and sensitivity.
CONCLUSION: The development of a new robust endothelial graft model expressing human tumor vascular proteins will help accelerate the development of novel theranostics targeting the tumor vasculature, which exhibit affinity specifically to human targets but not their murine counterparts. Our results also demonstrate the theranostic potential of MORAb-004 as PET imaging tracer and naked antibody therapy for TEM1-positive tumor.
Pubmed
Web of science
Création de la notice
03/03/2015 19:26
Dernière modification de la notice
03/03/2018 18:25
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