FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308407010> ?p ?o ?g. }

• W4308407010 abstract "<h3>Background</h3> Fibroblast Activation Protein (FAP) has been described as the “next billion-dollar nuclear theranostics target”¹, since more than 28 different tumor types have successfully been imaged in patients with radiolabeled FAP ligands. ^2-3 FAP can be found in the tumor microenvironment (TME) of most malignant solid tumors, while being absent in most healthy tissues. Thus, it is an attractive target for both imaging and therapeutic applications. Monoclonal antibodies targeting TME antigens have been considered for the delivery of bioactive payloads, such as proinflammatory cytokines. Antibody-cytokine fusions (also called immunocytokines) may exploit the tumor-homing properties of the antibody moiety, in order to concentrate the cytokine payload at the site of disease and enhance the therapeutic index.⁴ Interleukin-12 (IL12) have been extensively studied in oncology. IL12 strongly promotes NK cells, CD4+ and CD8+ T cells to produce interferon-gamma (IFN-g), one of the most relevant mediators of anti-cancer immunity.⁵ <h3>Methods</h3> In this work, we describe the generation of a novel anti-FAP antibody, called 7NP2. The tumor recognition properties of the antibody were validated by immunofluorescence procedures performed on cancer biopsies from human patients. A fusion protein consisting of the 7NP2 antibody linked to interleukin-12 was generated and the anti-cancer activity of the murine surrogate product (named mIL12-7NP2) was evaluated in mouse models. To prepare for future clinical trials, a fusion protein consisting of human IL12 linked to the 7NP2 antibody was further investigated in a toxicology study in <i>Cynomolgus</i> monkeys. <h3>Results</h3> Biodistribution analysis in tumor bearing mice confirmed the ability of the product to selectively localize to solid tumors while sparing healthy organs. Encouraged by these results, therapy studies were conducted <i>in vivo</i>, showing a potent anti-tumor activity in immunocompetent and immunodeficient mouse models of cancer, both as single agent and in combination with immune checkpoint inhibitors. The fully human product was tolerated when administered to non-human primates. <h3>Conclusions</h3> The results obtained in this work provided a rationale for future clinical translation activities using IL12-7NP2. <h3>References</h3> Calais J. FAP: The next billion dollar nuclear theranostics target?. <i>Journal of Nuclear Medicine</i> 2020;<b>61</b>(2). doi:10.2967/jnumed.119.241232. Kratochwil C, <i>et al</i>, 68Ga-FAPI PET/CT: Tracer uptake in 28 different kinds of cancer. <i>Journal of Nuclear Medicine</i> 2019;<b>60(</b>6). doi: 10.2967/jnumed.119.227967. Backhaus P, <i>et al</i>.Translational imaging of the fibroblast activation protein (FAP) using the new ligand [68Ga]Ga-OncoFAP-DOTAGA. <i>European Journal of Nuclear Medicine and Molecular Imaging</i> 2022;<b>49</b>(6). doi:10.1007/s00259-021-05653-0. Neri D. Antibody–Cytokine Fusions: Versatile Products for the Modulation of Anticancer Immunity. <i>Cancer Immunology Research</i> 2019. doi: 10.1158/2326-6066.CIR-18-0622. Puca E, <i>et al</i>. The antibody-based delivery of interleukin-12 to solid tumors boosts NK and CD8+ T cell activity and synergizes with immune checkpoint inhibitors. <i>International Journal of Cancer</i> 2019. doi:10.1002/ijc.32603. <h3>Ethics Approval</h3> Mouse experiments were performed under a project license (license number 04/2018) granted by the Veterinäramt des Kantons Zürich, Switzerland, in compliance with the Swiss Animal Protection Act (TSchG) and the Swiss Animal Protection Ordinance (TSchV). Procedures on Cynomolgus monkeys (including housing, health monitoring, restrain, dosing, etc) and ethical revision were performed according to the current Italian legislation (Legislative Decree March 4th, 2014 n. 26) enforcing the 2010/63/EU Directive on the protection of animals used for biomedical research." @default.
• W4308407010 created "2022-11-11" @default.
• W4308407010 creator A5002893098 @default.
• W4308407010 creator A5003031121 @default.
• W4308407010 creator A5007857615 @default.
• W4308407010 creator A5008175617 @default.
• W4308407010 creator A5016911189 @default.
• W4308407010 creator A5017038984 @default.
• W4308407010 creator A5017177249 @default.
• W4308407010 creator A5020168745 @default.
• W4308407010 creator A5036043878 @default.
• W4308407010 creator A5039170943 @default.
• W4308407010 creator A5039926073 @default.
• W4308407010 creator A5044693655 @default.
• W4308407010 creator A5047780528 @default.
• W4308407010 creator A5048952935 @default.
• W4308407010 creator A5049153656 @default.
• W4308407010 creator A5050215401 @default.
• W4308407010 creator A5054202974 @default.
• W4308407010 creator A5055386220 @default.
• W4308407010 creator A5060869891 @default.
• W4308407010 creator A5067376243 @default.
• W4308407010 creator A5091588711 @default.
• W4308407010 date "2022-11-01" @default.
• W4308407010 modified "2023-10-18" @default.
• W4308407010 title "1093 A novel IL12-based immunocytokine targeting fibroblast activation protein (FAP) for the treatment of cancer" @default.
• W4308407010 doi "https://doi.org/10.1136/jitc-2022-sitc2022.1093" @default.
• W4308407010 hasPublicationYear "2022" @default.
• W4308407010 type Work @default.
• W4308407010 citedByCount "0" @default.
• W4308407010 crossrefType "proceedings-article" @default.
• W4308407010 hasAuthorship W4308407010A5002893098 @default.
• W4308407010 hasAuthorship W4308407010A5003031121 @default.
• W4308407010 hasAuthorship W4308407010A5007857615 @default.
• W4308407010 hasAuthorship W4308407010A5008175617 @default.
• W4308407010 hasAuthorship W4308407010A5016911189 @default.
• W4308407010 hasAuthorship W4308407010A5017038984 @default.
• W4308407010 hasAuthorship W4308407010A5017177249 @default.
• W4308407010 hasAuthorship W4308407010A5020168745 @default.
• W4308407010 hasAuthorship W4308407010A5036043878 @default.
• W4308407010 hasAuthorship W4308407010A5039170943 @default.
• W4308407010 hasAuthorship W4308407010A5039926073 @default.
• W4308407010 hasAuthorship W4308407010A5044693655 @default.
• W4308407010 hasAuthorship W4308407010A5047780528 @default.
• W4308407010 hasAuthorship W4308407010A5048952935 @default.
• W4308407010 hasAuthorship W4308407010A5049153656 @default.
• W4308407010 hasAuthorship W4308407010A5050215401 @default.
• W4308407010 hasAuthorship W4308407010A5054202974 @default.
• W4308407010 hasAuthorship W4308407010A5055386220 @default.
• W4308407010 hasAuthorship W4308407010A5060869891 @default.
• W4308407010 hasAuthorship W4308407010A5067376243 @default.
• W4308407010 hasAuthorship W4308407010A5091588711 @default.
• W4308407010 hasBestOaLocation W43084070101 @default.
• W4308407010 hasConcept C149532602 @default.
• W4308407010 hasConcept C154317977 @default.
• W4308407010 hasConcept C159654299 @default.
• W4308407010 hasConcept C202751555 @default.
• W4308407010 hasConcept C203014093 @default.
• W4308407010 hasConcept C2776107976 @default.
• W4308407010 hasConcept C502942594 @default.
• W4308407010 hasConcept C55493867 @default.
• W4308407010 hasConcept C71924100 @default.
• W4308407010 hasConcept C86803240 @default.
• W4308407010 hasConcept C8891405 @default.
• W4308407010 hasConceptScore W4308407010C149532602 @default.
• W4308407010 hasConceptScore W4308407010C154317977 @default.
• W4308407010 hasConceptScore W4308407010C159654299 @default.
• W4308407010 hasConceptScore W4308407010C202751555 @default.
• W4308407010 hasConceptScore W4308407010C203014093 @default.
• W4308407010 hasConceptScore W4308407010C2776107976 @default.
• W4308407010 hasConceptScore W4308407010C502942594 @default.
• W4308407010 hasConceptScore W4308407010C55493867 @default.
• W4308407010 hasConceptScore W4308407010C71924100 @default.
• W4308407010 hasConceptScore W4308407010C86803240 @default.
• W4308407010 hasConceptScore W4308407010C8891405 @default.
• W4308407010 hasLocation W43084070101 @default.
• W4308407010 hasOpenAccess W4308407010 @default.
• W4308407010 hasPrimaryLocation W43084070101 @default.
• W4308407010 hasRelatedWork W1572283981 @default.
• W4308407010 hasRelatedWork W1971992579 @default.
• W4308407010 hasRelatedWork W2411114470 @default.
• W4308407010 hasRelatedWork W3030649553 @default.
• W4308407010 hasRelatedWork W3048051248 @default.
• W4308407010 hasRelatedWork W3190607176 @default.
• W4308407010 hasRelatedWork W3214265212 @default.
• W4308407010 hasRelatedWork W4200563690 @default.
• W4308407010 hasRelatedWork W4286629873 @default.
• W4308407010 hasRelatedWork W4321368025 @default.
• W4308407010 isParatext "false" @default.
• W4308407010 isRetracted "false" @default.
• W4308407010 workType "article" @default.