[\/et_pb_toggle][et_pb_toggle title=”Constructe de tip CAR (receptor himeric de antigen) care recunosc antigenele CD19, EGFR \u0219i PD-L1, inserate \u00een plasmide de tip lentiviral \u0219i \u00eempachetate \u00een particule lentivirale care pot fi folosite pentru ob\u021binerea unor celule de tip CAR-NK sau CAR-T.” open_toggle_text_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ open_toggle_background_color=”#FFFFFF” closed_toggle_background_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ icon_color=”#FFFFFF” open_icon_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ _builder_version=”4.23.1″ _module_preset=”default” title_text_color=”#FFFFFF” title_level=”h4″ title_font=”|600|||||||” border_radii=”on|15px|15px|15px|15px” border_style_all=”none” global_colors_info=”{%22gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473%22:%91%22open_icon_color%22,%22open_toggle_text_color%22,%22closed_toggle_background_color%22,%22closed_toggle_background_color%22,%22open_toggle_text_color%22,%22open_icon_color%22,%22closed_toggle_background_color%22,%22open_toggle_text_color%22,%22open_icon_color%22%93}” box_shadow_style=”preset3″]<\/p>\n
Antigen binding domain<\/strong><\/td>\n| Hinge field<\/strong><\/td>\n | Transmembrane domain<\/strong><\/td>\n | \n | field<\/strong><\/p>\n co-stimulator<\/strong><\/p>\n<\/td>\n Table 1. CAR constructs recognizing tumor antigens CD19, EGFR and PD-L1 containing different transmembrane domains and NK cell-specific co-stimulators<\/p>\n Map of a lentiviral vector indicating functional regions of the vector and relevant domains of the CAR construct<\/p>\n Cytotoxic activity of NK-92 cells transduced with an anti-CD19 CAR construct was assessed by determining cytolysis observed following contact of effector cells with fluorescently labeled tumor target cells. For this purpose, CD19- (U266) or CD19+ (NALM6) tumor cells in suspension were used as targets. Thus, it could be observed that the transduced cells specifically destroy, in a significantly increased proportion (**, p=0.0031), CD19+ NALM-6 tumor cells.<\/p>\n Cytotoxicity assays with untransduced NK-92 cells or transduced with anti-CD19 CAR against target cells expressing or not expressing the CD19 antigen. In the upper panel, CD19 antigen expression is determined by flow cytometry.<\/p>\n [\/et_pb_toggle][et_pb_toggle title=”Constructe CAR universale care con\u021bin un modul de legare al receptorului de imunoglobuline de mare afinitate Fc\u03b3RI (CD64), ce pot media r\u0103spunsul citotoxic prin anticorpi monoclonali cu diferite specificit\u0103\u021bi” open_toggle_text_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ open_toggle_background_color=”#FFFFFF” closed_toggle_background_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ icon_color=”#FFFFFF” open_icon_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ _builder_version=”4.23.1″ _module_preset=”default” title_text_color=”#FFFFFF” title_level=”h4″ title_font=”|600|||||||” border_radii=”on|15px|15px|15px|15px” border_style_all=”none” global_colors_info=”{%22gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473%22:%91%22open_icon_color%22,%22open_toggle_text_color%22,%22closed_toggle_background_color%22,%22closed_toggle_background_color%22,%22open_toggle_text_color%22,%22open_icon_color%22,%22closed_toggle_background_color%22,%22open_toggle_text_color%22,%22open_icon_color%22%93}” box_shadow_style=”preset3″]<\/p>\n field<\/strong><\/p>\n co-stimulator<\/strong><\/p>\n<\/td>\n Table 2. CAR constructs with Fc receptor binding mode<\/p>\n These universal CARs are based on the use of the extracellular domain of the high-affinity receptor of the Fc constant domains of IgG immunoglobulins (CD64), and various transmembrane and intracytoplasmic modules. The use of these CARs based on the extracellular domain of high-affinity Fc receptors allows the "arming" of NK or T cells with various monoclonal antibodies or protein modules that recognize specific antigens, coupled to the Fc domain, giving these cells the flexibility to be personalized (used against various antigens). In addition, the specificity of these genetically modified cells can be optimized by conjugation with multiple antibodies, thereby creating cells with multivalent specificities. The use of a common backbone, CD64 or a common epitope tag (myc-tag), in the construction of these chimeric receptors allows, in addition, the easy detection of their expression on the surface of genetically modified cells.<\/p>\n To demonstrate the functionality of universal CAR receptors that can bind antibody molecules with therapeutic potential, we performed a cytotoxicity assay against Raji cells expressing CD20 and CD19 antigens with untransduced NK-92 cells or transduced with anti-CD19 CAR or CAR containing CD16(F158V) or CD64 high-affinity binding modules, in the absence or presence of therapeutic IgG1 anti-CD20 antibodies, Rituximab.<\/p>\n Determination of cytotoxic activity against Raji cells (CD19+<\/sup>CD20+<\/sup>) in the presence or absence of anti-CD20 antibodies of untransduced and transduced NK-92 cells with different CAR, anti-CD19 or universal constructs. The ratio of effector to target cells was 3:1.<\/p>\n [\/et_pb_toggle][et_pb_toggle title=”Vectori lentivirali cu constructe CAR care co-exprim\u0103 interleukine \u0219i permit multiplicarea \u0219i supravie\u021buirea celulelor NK-92 in vitro independent de citokine exogene.” open_toggle_text_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ open_toggle_background_color=”#FFFFFF” closed_toggle_background_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ icon_color=”#FFFFFF” open_icon_color=”gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473″ _builder_version=”4.23.1″ _module_preset=”default” title_text_color=”#FFFFFF” title_level=”h4″ title_font=”|600|||||||” border_radii=”on|15px|15px|15px|15px” border_style_all=”none” global_colors_info=”{%22gcid-2dd42c1b-4a6d-4417-9dc5-a03359dc6473%22:%91%22open_icon_color%22,%22open_toggle_text_color%22,%22closed_toggle_background_color%22,%22closed_toggle_background_color%22,%22open_toggle_text_color%22,%22open_icon_color%22,%22closed_toggle_background_color%22,%22open_toggle_text_color%22,%22open_icon_color%22%93}” box_shadow_style=”preset3″]Vectorii care exprim\u0103 un construct CAR universal de tip CD64 \u0219i interleukina 2 sau 15 de pe acela\u0219i vector au fost \u00eempacheta\u021bi \u00een particule lentivirale \u0219i folosi\u021bi pentru transduc\u021bia celulelor NK-92. Celulele care exprim\u0103 IL-15 au demonstrat capacitate de autoselec\u021bie \u0219i proliferare \u00een absen\u021ba IL-2 \u00een mediul de cultur\u0103.<\/p>\n [\/et_pb_toggle][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=\u201d4.23\u2033 _module_preset=\u201ddefault\u201d global_colors_info=\u201d{}\u201d][et_pb_column type=\u201d4_4\u2033 _builder_version=\u201d4.23\u2033 _module_preset=\u201ddefault\u201d global_colors_info=\u201d \u201d{}\u201d][et_pb_text _builder_version=\u201d4.23.1\u2033 _module_preset=\u201ddefault\u201d global_colors_info=\u201d{}\u201d]Resulting patents <\/strong>following the CAR-NK project<\/strong><\/p>\n <\/p>\n Publications resulting from the CAR-NK project<\/strong><\/p>\n *The articles identified in positions 5 and 8 were made in cooperation with private entities.<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>","protected":false},"excerpt":{"rendered":" Technological Transfer NK92 cells transduced with a vector co-expressing a CD64-2A CAR construct and interleukin 2 capable of producing IL2, thus becoming independent of the presence of interleukin NK92 cells transduced with a vector co-expressing a CD64-2A CAR construct and interleukin 15 capable to produce IL15, thus becoming independent of the presence of exogenous interleukin. NK92 cells transduced with [\u2026]<\/p>","protected":false},"author":2,"featured_media":0,"parent":101504,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","inline_featured_image":false,"footnotes":""},"class_list":["post-101585","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/pages\/101585","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/comments?post=101585"}],"version-history":[{"count":18,"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/pages\/101585\/revisions"}],"predecessor-version":[{"id":101841,"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/pages\/101585\/revisions\/101841"}],"up":[{"embeddable":true,"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/pages\/101504"}],"wp:attachment":[{"href":"https:\/\/oncogen.ro\/en\/wp-json\/wp\/v2\/media?parent=101585"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}} |
![\"\"](\"https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/12\/harta-300x140.png\")
<\/p>\n![\"\"](\"https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/12\/grafic-300x210.png\")
<\/p>\n![\"\"](\"https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/12\/celule-300x175.png\")
<\/p>\n![\"\"](\"https:\/\/oncogen.ro\/wp-content\/uploads\/2023\/12\/tabel-citotoxicitate-300x170.png\")
<\/p>\n