Abstract: Endometriosis is a chronic inflammatory systemic sex hormone-dependent gynecological disease, characterized by the presence and growth of endometrial tissue (glands and stroma) outside the uterine cavity, predominantly, but not exclusively, in the pelvic compartment. Here, the inventors show that the use of Neuropilin/VEGF binding inhibitors, so called, Neuropilin antagonist (NRPa), bring new perspective to treat and cure endometriosis in women suffering thereof. NRPa alone is efficient to inhibit primary endometrial cell proliferation and apoptosis/necrosis program cell death of targeted cells. The effective NRPa concentration needed is very low (NRPa-48 IC50=10?7M) and is dependent of the NRPa structure. Moreover, the association of NRPa with progestogen drug increases the anti-proliferative effect. Therefore, the present invention relates to the use of neuropilin antagonists for the treatment of endometriosis.

Abstract: Neuropilin-1 is henceforth a relevant target in cancer treatment, however way-of-action is remains partly elusive and the development of small inhibitory molecules is therefore required for its study. Here, the inventors report that two neuropilin small-sized antagonists (NRPa-47, NRPa-48), VEGF-A165/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in triple negative breast cancer cell line (MDA-MB-231). In particular, the inventors showed for the first time, how NRPa may altered tumor cell signaling and contributed in the down-modulation of the cancer therapeutic key factor p38?-kinase phosphorylation. More importantly, the association of NRPa with a p38? inhibitor leads to additional and/or synergistic effect of these drugs (depending of the dose used) for significantly reducing breast cancer cell proliferation Thus, the efficient association of NRPa and p38?-kinase inhibitors are thus credible for the treatment of cancer.

Abstract: A number of anti-angiogenic strategies connected with the VEGF signalling pathway are used in current clinical treatment or trial phase, but they either cause adverse effects or are not specific. Various strategies were aimed at identifying peptides inhibiting the VEGF-A165/NRP-1 interaction. A well-known antiangiogenic peptide is the heptapeptide termed “A7R” having the amino acid sequence ATWLPPR, for which various derivatives have been synthesized, which include peptides having the general sequence Lys(hArg)-AA2-AA3-Arg. However, the ability of the known peptides to inhibit the VEGF-A165/NRP-1 interaction was too low for their use as candidate drugs for inhibiting angiogenesis in subjects in need thereof. The present inventors have now conceived a family of novel peptide-like compounds having a nanomolar affinity for NRP-1, which are thus endowed with a powerful capacity to inhibit the VEGF-A165/NRP-1 interaction.

Abstract: Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells QI predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g.

Abstract: This invention relates to a composition comprising oligoproanthocyanidins (OPC) and omega-3 fatty acids, for use in preventing or stabilizing the development and/or the progression of a diabetes-related eye condition in a subject; this invention includes a functional food, a nutraceutical composition or a food or dietary supplement comprising said composition; this invention also relates to a pharmaceutical composition or a veterinarian product comprising oligoproanthocyanidins (OPC) and omega-3 fatty acids.

Abstract: The invention relates to a composition comprising an enzyme selected from the group comprising superoxide dismutase (SOD) and SOD mimics and the like, in association with lutein and at least one stereoisomer of zeaxanthin; the invention also includes a kit of parts comprising such composition, wherein the kit comprises a first part comprising the enzyme, and a second part comprising lutein and at least one zeaxanthin isomer; according to the invention, the composition or the kit of part may be included in a functional food, a nutraceutical composition or a food or dietary supplement, a medicament or a pharmaceutical composition, or a veterinarian product; the invention also relates to a composition for use in treating, preventing or stabilizing a disease, condition or disorder of the eye associated to oxidative stress, comprising administering to a subject in need thereof a medicament or a pharmaceutical composition according to the invention.

Abstract: The present invention relates to a composition comprising a natural extract containing anthocyanins and an agent for enhancing vigilance, and to a method for alleviating visual discomfort related to or caused by oxidative stress comprising administering via transmucosal route the composition of the invention, said composition being in a form adapted to transmucosal administration, said form preferably being a chewing gum, an orodispersible/orodisintegrating tablet or film or a buccal spray.

Abstract: The invention relates to the monoclonal antibody A24 directed against the transferrin receptor. This antibody is in particular useful as an antiproliferative agent.

Abstract: Abstract The invention relates to the monoclonal antibody A24 directed against the transferrin receptor This antibody is in particular useful as an antiproliferative agent.

Abstract: Vitamin A (retinol) deficiency results in impaired response to infection and increased mortality. By the present invention, we show that retinol activates immature dendritic cells (DC) and enhances antigen presentation via a cross-talk with inflammatory cytokines, whereas it increases DC death in the absence of these cytokines. These effects, that are mediated through retinoic acids and distinct nuclear retinoid receptor pathways, can be dissociated from each other with selective synthetic retinoids. The present invention identifies a novel cellular target and function for retinoids, provides compositions and methods for modulating the immune system and for treating or preventing various physical disorders in animals, preferably via controlling activation and/or apoptosis in antigen-presenting cells using selective retinoids.