Abstract: The present invention relates to novel therapeutic combinations comprising an oxazaphosphorine derivative and an immune checkpoint modulator for the treatment or the prevention of cancers.

Abstract: The inventors herein show that purinergic receptors regulate the conversion of macrophage pro-inflammatory reprogramming into anti-inflammatory phenotype in patients suffering from COVID-19 disease. Moreover, they show that P2Y receptor agonists repress NLRP3 inflammasome-dependent IL-1b secretion, but also impair the replication and the cytopathogenic effects of SARS-CoV-2. These results therefore suggest that some purinergic receptors agonists can treat acute lung injury and respiratory disease that are associated with SARS-CoV-2 infection. In addition, their results show that antagonists of the purinergic receptors P2X impair the replication of said virus. The present invention therefore proposes to use purinergic receptors modulators and NLR3-P2Y2R immune checkpoint modulators to treat patients suffering from a virus-induced acute respiratory distress syndrome.

Abstract: The present disclosure relates to the field of nanomedicine, in particular for treating cancers. The present disclosure more specifically provides new methods of treating undesirable M2-polarized macrophages and/or inducing M1 macrophage polarization in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of nanoparticles containing metallic elements.

Abstract: The present invention relates to the field of medical devices, more particularly the field of devices for extracting circulating molecules from the blood of a mammal, and their therapeutic uses, in particular in treating sepsis, cytokine release syndrome and/or any other form of systemic inflammatory response or cytokine shock, caused by bacterial, parasitic, fungal or viral infections, in particular caused by a viral infection, for example coronaviruses with human respiratory tract tropism.

Abstract: Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here the present inventors show that ionizing radiation induces the expression of interferon-regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. They reveal that the activation of the Ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with ?-interferon, lipopolysaccharide or chemotherapeutic agent (such as cis-platin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a proinflammatory phenotype. They further demonstrate that NADPH oxidase 2 (NOX2)-dependent ROS production is upstream to ATM activation and is essential during this process.

Abstract: The present invention is drawn to the use of Minaprine dihydrochloride and analogs thereof, for reducing tumor growth when administered to a patient suffering from cancer.

Abstract: The present invention is drawn to the use of the compounds highlighted in Tables 1 & 2 and analogs thereof, for enhancing IR-mediated cellular cannibalism in cancer cells. Said compounds are herein called “enhancers of IR-mediated cellular cannibalism”. They can be used to enhance tumor immunogenicity and/or to induce a significant protective anticancer immune response in subjects that will receive or that have received a radiotherapy treatment. In other words, said compounds can be used to potentiate a radiotherapy treatment in a subject in need thereof. Said compounds are preferably chosen in the group consisting of: Mebhydroline 1,5-napthalene disulfonate salt, Flurbiprofen, Minaprine dihydrochloride, Myricetin, Digoxin, Digitoxin, Lanatoside, LOPA87, VP331, RN-1-026, SG6163F, VP450, and VP43.

Abstract: Identification of effective targets alleviating the programmed cell removal (PrCR) of tumor cells by macrophages is of very high interest. The present inventors have identified that the cyclin-dependent kinase inhibitor p21 protein is a strong regulator of the macrophage-mediated PrCR. Also, they showed that the adoptive transfer of p21 overexpressing monocytes induces macrophage PrCR and transition from an anti-inflammatory to a pro-inflammatory phenotype in vivo, delays cancer progression and increases significantly the overall survival of mice engrafted with cancer cells. The present invention therefore concerns therapeutic compositions comprising monocytes that over-express the cyclin-dependent kinase inhibitor p21 protein, and their use for treating mammals suffering from cancer, especially leukemia.

Abstract: The invention relates to methods for treating tumors. In particular, the invention provides novel use of nanoparticles in combination with ionizing radiations for treating tumors, wherein the combined effect of nanoparticles induces senescence and/or cannibalism of the tumor cells.

Abstract: The present inventors show that cannibal cells can undergo senescence after entosis in vivo and that the tumor suppressive protein p53 act as a repressor of this phenomenon. They therefore propose new tools to study the molecular pathways involved in the cannibalism process, for example by measuring the expression levels of p53 or splice variants thereof (such as ?133TP53, TP53?, TP53? or ?40TP53), the release of extracellular ATP or purinergic P2Y2 receptor activity. The present inventors also demonstrated that the detection of senescent cannibal cells in breast adenocarcinoma obtained from patients treated with neo-adjuvant therapy positively correlates with good patient's response to treatment. Altogether, these results provide the first evidence that detection of cellular cannibalism and senescence simultaneously in tumors helps for the diagnosis of disease outcomes and for the prediction of treatment efficiency against cancer diseases.

Abstract: The present invention is drawn to the use of Minaprine dihydrochloride and analogs thereof, for reducing tumor growth when administered to a patient suffering from cancer.

Abstract: The present invention relates to methods and pharmaceutical composition for modulation polarization and activation of macrophages. In particular, the present invention relates to methods for modulating macrophage M1/M2 polarization in a subject in need thereof comprising administering to the subject a therapeutically effective amount of P2Y2 receptor agonists or antagonists.

Abstract: Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here the present inventors show that ionizing radiation induces the expression of interferon-regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. They reveal that the activation of the Ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with ?-interferon, lipopolysaccharide or chemotherapeutic agent (such as cis-platin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a proinflammatory phenotype. They further demonstrate that NADPH oxidase 2 (NOX2)-dependent ROS production is upstream to ATM activation and is essential during this process.

Abstract: The present invention is drawn to the use of the compounds highlighted in Tables 1 & 2 and analogs thereof, for enhancing IR-mediated cellular cannibalism in cancer cells. Said compounds are herein called “enhancers of IR-mediated cellular cannibalism”. They can be used to enhance tumor immunogenicity and/or to induce a significant protective anticancer immune response in subjects that will receive or that have received a radiotherapy treatment. In other words, said compounds can be used to potentiate a radiotherapy treatment in a subject in need thereof. Said compounds are preferably chosen in the group consisting of: Mebhydroline 1,5-napthalene disulfonate salt, Flurbiprofen, Minaprine dihydrochloride, Myricetin, Digoxin, Digitoxin, Lanatoside, LOPA87, VP331, RN-1-026, SG6163F, VP450, and VP43.

Abstract: Disclosed is a composition for use in the prevention or treatment of a subject suffering from a cancer in combination with radiotherapy, wherein the composition includes a conjugate, eventually associated with pharmaceutically acceptable carrier, the conjugate including i) the Shiga Toxin B subunit (STxB), a fragment or a derivative thereof; and ii) at least one epitope associated with the cancer.

Abstract: The present invention relates to methods and pharmaceutical composition for modulation polarization and activation of macrophages. In particular, the present invention relates to methods for modulating macrophage M1/M2 polarization in a subject in need thereof comprising administering to the subject a therapeutically effective amount of P2Y2 receptor agonists or antagonists.

Abstract: The present invention provides methods and pharmaceutical compositions for treating human immunodeficiency virus type 1 (HIV-1) infections. In particular, the present invention relates to a method for treating HIV-1 infection in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an inhibitor of SGT1 activity or expression.

Abstract: Disclosed is a composition for use in the prevention or treatment of a subject suffering from a cancer in combination with radiotherapy, wherein the composition includes a conjugate, eventually associated with pharmaceutically acceptable carrier, the conjugate including i) the Shiga Toxin B subunit (STxB), a fragment or a derivative thereof; and ii) at least one epitope associated with the cancer.

Abstract: The present inventors show that cannibal cells can undergo senescence after entosis in vivo and that the tumor suppressive protein p53 act as a repressor of this phenomenon. They therefore propose new tools to study the molecular pathways involved in the cannibalism process, for example by measuring the expression levels of p53 or splice variants thereof (such as ?133TP53, TP53?, TP53? or ?40TP53), the release of extracellular ATP or purinergic P2Y2 receptor activity. The present inventors also demonstrated that the detection of senescent cannibal cells in breast adenocarcinoma obtained from patients treated with neo-adjuvant therapy positively correlates with good patient's response to treatment. Altogether, these results provide the first evidence that detection of cellular cannibalism and senescence simultaneously in tumors helps for the diagnosis of disease outcomes and for the prediction of treatment efficiency against cancer diseases.

Abstract: The present invention provides methods and pharmaceutical compositions for treating human immunodeficiency virus type 1 (HIV-1) infections. In particular, the present invention relates to a method for treating HIV-1 infection in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an inhibitor of SGT1 activity or expression.