Three clinical-stage tumor targeting antibodies reveal differential expression of oncofetal fibronectin and tenascin-C isoforms in human lymphoma.
The antibody-based targeted delivery of bioactive molecules to tumor vasculature is an attractive avenue to concentrate therapeutic agents at cancer sites, while sparing normal organs. L19, F8 and F16 are clinical-stage human monoclonal antibodies, which selectively recognize splice isoforms of fibronectin and tenascin-C in the modified extracellular matrix of neoplastic lesions. Here, we report the first comparative immunohistochemical analysis of L19, F8 and F16 in human Hodgkin and non-Hodgkin lymphomas. F16 was found to strongly stain the majority of lymphomas but also specimens of nonspecific lymphadenitis. By contrast, L19 exhibited a better discrimination between tumoral and inflammatory processes, yet at the expense of a weaker staining of the majority of lymphoma specimens investigated. The staining patterns observed for F8 were intermediate between the ones observed for L19 and F16. This study provides a rationale basis for the clinical investigation of therapeutic derivatives of the three antibodies in lymphoma patients.
Schliemann
Christoph
C
Institute of Pharmaceutical Sciences, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
Wiedmer
Andrea
A
Pedretti
Marta
M
Szczepanowski
Monika
M
Klapper
Wolfram
W
Neri
Dario
D
D000911:Antibodies, Monoclonal / Q000276:immunology*; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000378:metabolism*; D020033:Protein Isoforms / Q000276:immunology / Q000378:metabolism*; D019063:Tenascin / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D020033:Protein Isoforms; D019063:Tenascin; C121542:oncofetal fibronectin