Onconox Aps

Merck Serono S. a.

Ribovax Biotechnologies S.a.

Ganial Immunotherapeutics, Inc.

Gianni Garotta

Yousef Al-Abed

Ferdinando Nicoletti

Michel Dreano

Ada Funaro

Marianne Murphy

Guido Tiberio

Luisa Schiaffonati

HIV-protease inhibitors, particularly saquinavir, showed strong anticancer activity but numerous side effects limited its application. In order to overcome its toxicity original compounds were modified by covalent attachment of NO. The efficacy of parental and NO-modified drug was compared in vitro and in vivo. Anticancer activities of NO-modified saquinavir (Saq-NO) was monitored in vitro using assay for cell viability, proliferation, necrotic, autophagic and apoptotic cell death, differentiation, expression of intracellular molecules such as cyclin D3, p53 and Akt. Antitumor properties and toxicity of the compound was estimated in vivo. Saq-NO abrogated the viability of large spectrum of human and rodent tumor cell lines with IC50 significantly lower than parental drug and expressed strong antimelanoma action in vivo. In contrast to saquinavir, there was no detectable toxicity against primary cells in vitro and in vivo. Saq-NO permanently diminished cell proliferation by induction of cell cycle block accompanied with minor presence of tumor cell death. Repressed proliferation was coordinated with strong activation of p53 and differentiation of C6 and B16 cells into oligodendrocytes or 'Schwan' like cells, respectively. Oppositely to general characteristic of saquinavir to inhibit Akt signalling, Saq-NO treatment resulted in transient and intensive upregulation of Akt. This antagonism between parental and modified compound could be the crucial for switch of saquinavir from toxic to completely untoxic drug.

Antitumor properties of NO modified protease inhibitors

The present Invention provides novel methods for immortalizing cells that secrete antibodies of one or more specific isotypes. Polyclonal, oligoclonal, and monoclonal populations of cells obtained using the methods of the Invention can be screened on the basis of the functional and/or binding activities of the antibodies they secrete, for example directed to antigens of human or viral origin having medical interest, in cell culture conditions. Using these methods, human B cells that secrete antibodies binding human Cytomegalovirus, Herpes Simplex Virus, or HSP60 protein have been efficiently immortalized with Epstein-Barr virus.

Methods for obtaining immortalized antibody secreting cells

The present invention relates to an isoxazole derivative, the compound of formula (I) 

(S,R)-3-phenyl-4,5 dihydro-5-isoxazole acetic acid-nitric oxide and use thereof as anti-cancer and antiviral agent

The invention relates to the use of IL-6 in liver cirrhosis.

Use of IL-6 in liver injury

Growing community of inventors

Lucinges, France

Gianni Garotta