A first aspect of the present invention refers to an antibody, preferably a monoclonal antibody, recognizing the extracellular domain of NG2/CSPG4 and its ability to induce apoptosis and/or autophagy upon antigen-binding in cancer cells expressing NG2/CSPG4. 10 Therefore, the antibody of the invention can be used for cell growth inhibition by exposing a cell expressing NG2/CSPG4 to a therapeutic amount of an antibody capable of binding to NG2/CSPG4. A second aspect of the present invention refers to a pharmacological composition comprising a therapeutic amount of the antibody, in its entirety or single chain variable 15 fragment (scFv) of the invention that is active against NG2/CSPG4, or any other portion of the antibody, preferably, embodied in a bispecific antibody construct (e.g. an antibody binding both NG2/CSPG4 and another cell surface molecule and/or antigen) or a fusion protein comprised of a therapeutic amount of the antibody, in its entirety or single chain variable fragment, or scFv, an another therapeutic molecule, such as a cytochine or an 20 aptoptosis-inducing agent (e.g TRAIL or Fas Ligand), or a CAR T (Chimeric Antigen Receptor T cell) construct in which the scFv derived from the portion of the antibody of the invention is expressed on the surface of a CAR T cell, such as to simultaneously engaging NG2/CSPG4 expressing cells and endogenous T cells and favor the maintenance of the CAR T cell in proximity to the cancer cell to trigger the activation of 25 the engaged T cell. Further provided by the invention is the use of the antibody and the composition of the invention for selective trigger of apoptosis and/or autophagy in cells specifically expressing NG2/CSPG4 recognized by the antibody. A further aspect of present invention refers to the antibody and the composition of the 30 invention for use in the treatment of an apoptosis and/or autophagy-dependent disease, preferably cancer, more preferably solid or hematological cancers, as well as cancerrelated diseases.
Pro-apoptotic anti-NG2/CSPG4 monoclonal antibodies for disease therapy / Perris, R; Dallatomasina, A; Tamburini, E; Nicolosi, Pa; Mucignat, Mt. - ELETTRONICO. - (2019).
Pro-apoptotic anti-NG2/CSPG4 monoclonal antibodies for disease therapy
Perris R
Conceptualization
;Dallatomasina AFormal Analysis
;Tamburini EFormal Analysis
;
2019-01-01
Abstract
A first aspect of the present invention refers to an antibody, preferably a monoclonal antibody, recognizing the extracellular domain of NG2/CSPG4 and its ability to induce apoptosis and/or autophagy upon antigen-binding in cancer cells expressing NG2/CSPG4. 10 Therefore, the antibody of the invention can be used for cell growth inhibition by exposing a cell expressing NG2/CSPG4 to a therapeutic amount of an antibody capable of binding to NG2/CSPG4. A second aspect of the present invention refers to a pharmacological composition comprising a therapeutic amount of the antibody, in its entirety or single chain variable 15 fragment (scFv) of the invention that is active against NG2/CSPG4, or any other portion of the antibody, preferably, embodied in a bispecific antibody construct (e.g. an antibody binding both NG2/CSPG4 and another cell surface molecule and/or antigen) or a fusion protein comprised of a therapeutic amount of the antibody, in its entirety or single chain variable fragment, or scFv, an another therapeutic molecule, such as a cytochine or an 20 aptoptosis-inducing agent (e.g TRAIL or Fas Ligand), or a CAR T (Chimeric Antigen Receptor T cell) construct in which the scFv derived from the portion of the antibody of the invention is expressed on the surface of a CAR T cell, such as to simultaneously engaging NG2/CSPG4 expressing cells and endogenous T cells and favor the maintenance of the CAR T cell in proximity to the cancer cell to trigger the activation of 25 the engaged T cell. Further provided by the invention is the use of the antibody and the composition of the invention for selective trigger of apoptosis and/or autophagy in cells specifically expressing NG2/CSPG4 recognized by the antibody. A further aspect of present invention refers to the antibody and the composition of the 30 invention for use in the treatment of an apoptosis and/or autophagy-dependent disease, preferably cancer, more preferably solid or hematological cancers, as well as cancerrelated diseases.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
