Abstract: Today, despite current advances in combinatorial therapies such as surgery, radiotherapy and chemotherapy, aggressive cancers remain fatal. Cancer stem-like cells (CSCs) may account for chemotherapy resistance and thus represent a promising therapeutic target. In this context, the present inventors identified essential intracellular pathways favoring the self-renewal and survival of CSCs. More precisely, the present inventors showed that the cytokine co-receptor GP130 acts as a co-receptor for Apelin/APJ signaling and that the interaction of Apelin with APJ/GP130 activates a dual signaling pathway involving the Akt/mTOR and STAT3 transcription factor, thereby promoting CSCs survival and self-renewal. They therefore propose to block these pathways in order to treat patients suffering from tumors containing CSCs, such as glioblastomas. In another aspect, the invention relates to the use of the Apelin expression level for evaluating the survival probability of a subject suffering from glioblastoma.

Abstract: The invention relates to recombinant monovalent antibodies which are heterodimers of a first protein chain comprising the variable domain of the heavy chain of an antibody of interest and the CH2 and CH3 domains of an IgG immunoglobulin and a second protein chain comprising the variable domain of the light chain of said immunoglobulin of interest and the CH2 and CH3 domains of said IgG immunoglobulin. These antibodies can be used in particular as therapeutic agents in all cases where monovalent binding to a ligand such a cellular receptor is required.