Junctional adhesion molecule-C (JAM-C) binding compounds and methods of their use

#The instant invention relates to the treatment of cancer, in particular brain cancer. More specifically the invention relates to the treatment of glioma with compounds that specifically bind to JAM-B or JAM-C, such as antibodies and antagonists specifically binding to JAM-B or JAM-C.

#Gliomas

#The major cell types of the brain are neurons, oligodendrocytes, which are the cells forming the myelin sheaths around neuronal axons in the Central Nervous System (CNS), and astrocytes, the cells supporting both neuron and oligodendrocyte functions. Oligodendrocytes and astrocytes, together with ependymal cells that line the ventricular system, constitute the glia, the specialised connective tissue of the CNS.

#FIG. 1: JAM-C expression in human gliomas. A. RT-PCR for human JAM-C on glioma cell lines. Lanes 1, 6, 8: astrocytomas (grade III) Ge182, Ge299, Ge328 respectively, lanes 2, 3, 4, 5, 9: glioblastomas Ge224, Ge242, Ge258, Ge285, Ge360, respectively, lane 7: oligoastrocytoma Ge314. B. Cytofluorimetric analysis of JAM-C expression on Ge258 human glioblastoma cells. The histogram shows the profile obtained with the anti-JAM-C monoclonal antibody (black open curve) and the isotype control antibody (gray-filled curve). C. Immunoprecipitation of human JAM-C in Ge258 human glioblastoma cells. Lane 1: pre-immune rabbit serum, lane 2: polyclonal anti-human JAM-C.

#FIG. 2: Heterogeneous expression of JAM-C in human astrocytomas. A Ge 258 glioblastoma showing strong JAM-C expression on the great majority of tumour cells. B Ge 280 astrocytoma (grade III), single isolated tumour cells express high levels of JAM-C (indicated by an arrowhead), the arrow indicates a positive blood vessel. C Ge 305 glioblastoma where strong immunoreactivity for JAM-C is detected at the tumour margin with the normal brain. The arrow indicates a positive blood vessel, (T: tumour, N: normal brain). D Ge 299 astrocytoma (grade III) showing uniform JAM-C expression on all tumour cells. The arrow indicates a stained blood vessel. (Magnification: A 20× B 20×, C 20×, D 20×).

#FIG. 3: Expression of JAM-C at sites of cell-cell contacts and intra-tumor heterogeneity. A. Ge262 astrocytoma (Grade II) showing high levels of JAM-C expression at points of cell-cell contacts. B. Ge258 glioblastoma showing cells expressing high levels of JAM-C intermingled with cells negative for JAM-C expression. (Magnifications: A 40×, B 40×).

#The first aspect of the instant invention relates to use of a compound that specifically binds to JAM-C for the treatment of glioma.

#The first embodiment of the first aspect of the invention is the use of a compound that specifically binds to JAM-C for the treatment of glioma.

#The second embodiment of the first aspect of the invention is the use according to the first embodiment of the first aspect of the invention, wherein the compound is an antagonist of JAM-C.