Comparative immunohistochemical staining of atherosclerotic plaques using F16, F8 and L19: Three clinical-grade fully human antibodies.
OBJECTIVE
F16, F8 and L19 are three fully human monoclonal antibodies, specific to splice isoforms of tenascin-C and fibronectin, which stain sites of active tissue remodeling and which are currently in Phase I and II clinical trials as radio-immunoconjugates and immunocytokines in patients with cancer and arthritis. The characterization of atherosclerosis using these antibodies may open novel pharmacodelivery options for the imaging and treatment of cardiovascular conditions. It may also allow a better assessment of the corresponding immunoconjugates in polymorbid patients with atherosclerotic plaques.


METHODS
We performed a comparative immunohistochemical analysis with the F16, F8 and L19 antibodies in 28 freshly frozen human carotid plaques and in 11 normal arteries. Furthermore, we assessed the localization of the antibodies in relation to the infiltrating macrophages, vasa vasorum and Ki67-positive proliferating cells of the plaque.


RESULTS
The F16 antibody, specific to the extra-domain A1 of tenascin-C, stained plaques with a selective and intense pattern, while F8 and L19, specific to the EDA and EDB domains of fibronectin, respectively, exhibited a less selective and intense staining. In immunofluorescence, F16 was found to bind regions rich in macrophages, vasa vasorum and proliferating cells, while showing no detectable vs. weak staining of normal arteries and of quiescent plaque structures.


CONCLUSIONS
The human monoclonal antibody F16 stains areas of active tissue remodeling in atherosclerotic plaques and may thus deserve to be investigated as a suitable building block for the development of radiopharmaceuticals for plaque imaging or for the antibody-based targeted delivery of therapeutic agents to atherosclerotic lesions.
Pedretti
Marta
M
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Rancic
Zoran
Z
Soltermann
Alex
A
Herzog
Bernhard A
BA
Schliemann
Christoph
C
Lachat
Mario
M
Neri
Dario
D
Kaufmann
Philipp A
PA
D000368:Aged; D000906:Antibodies / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001158:Arteries / Q000378:metabolism; D001168:Arthritis / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007107:Immune System; D018796:Immunoconjugates / Q000737:chemistry; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism; D017434:Protein Structure, Tertiary
D000906:Antibodies; D000911:Antibodies, Monoclonal; D016207:Cytokines; D018796:Immunoconjugates