*** IBB - CNR *** Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134, Naples, Italy. Department of Gene Vectors, Helmholtz Center for Environmental Health, Munich, Germany. School of Medicine, Institute of Pathology, Department of Neuropathology, Technical University Munich, Munich, Germany. Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Universita Degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino Florence, Italy. Department of Otorhinolaryngology, Klinikum der Universitat Munchen, Munich, Germany. Electronic address: firstname.lastname@example.org.
6A10 is a CA XII inhibitory monoclonal antibody, which was demonstrated to reduce the growth of cancer cells in vitro and in a xenograft model of lung cancer. It was also shown to enhance chemosensitivity of multiresistent cancer cell lines, and to significantly reduce the number of lung metastases in combination with doxorubicin in mice carrying human triple-negative breast cancer xenografts. Starting from these data, we report here on the development of the 6A10 antigen-binding fragment (Fab), termed Fab6A10, and on its functional, biochemical and structural characterization. In vitro binding and inhibition assays demonstrated that Fab6A10 selectively binds and inhibits CA XII, whereas immunohistochemistry experiments highlighted its capability to stain malignant glioma cells in contrast to the surrounding brain tissue. Finally, the crystallographic structure of the CA XII/Fab6A10 complex provided insights into the inhibition mechanism of this Fab, showing that upon binding Fab6A10 obstructs the substrate access to the enzyme active site and interacts with His64 freezing it in its out conformation. Altogether, these data indicate Fab6A10 as a new promising therapeutic tool against cancer.<br>
237 Records (229 escludendo Abstract e Conferenze). Impact factor totale: 952.622 (927.315 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 969.535 (939.414 escludendo Abstract e Conferenze).