Khansa Yam'mapapo Yosakhala Yaing'ono: New Preclinical Data

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Written by Linda Hohnholz

Zotsatira zikuwonetsa kuti TriKE yolunjika ya mesothelin imatha kugwira ntchito limodzi ndi chisamaliro chapano ndikupereka phindu ngakhale m'malo a hypoxic a chotupa cholimba.

GT Biopharma, Inc., kampani yachipatala ya immuno-oncology yomwe imayang'ana kwambiri pakupanga zithandizo zatsopano zotengera kampani yomwe imapanga ma cell amtundu wa Tri-specific Natural killer (NK), nsanja yaukadaulo ya TriKE® protein biologic, idapereka chidziwitso chowonetsa buku lake la TriKE kuyendetsa NK. cell immunotherapy motsutsana ndi khansa yosakhala yaying'ono ya m'mapapo (NSCLC) mu hypoxic solid chotupa microenvironment ku ESMO's Targeted Anticancer Therapies Congress (TAT).

Gregory Berk, MD, Purezidenti wa R&D ndi Chief Medical Officer wa Company adati, "Umboni wotsimikizira izi ukuwonetsa, ngakhale pali kusiyana kwa ma cell achitetezo a Stage IVB NSCLC odwala, TriKE yoyang'aniridwa ndi mesothelin imatha kugwira ntchito limodzi ndi chisamaliro chapano komanso perekani phindu ngakhale m'malo a hypoxic a chotupa cholimba, chomwe chikuyenera kufufuzidwa mowonjezereka bukuli, lolunjika pa TriKE. "

Kuyendetsa NK cell immunotherapy motsutsana ndi NSCLC, mu nkhani ya hypoxia, pogwiritsa ntchito Tri-specific Killer Engager (TriKE®)

Mbiri - Pakali pano, Tri-specific killer engagers (TriKE®) akuyesedwa kuchipatala kuti athetse khansa ya m'magazi ndi lymphoma. TriKE's cross-link CD16/FcγRIII ndi chotupa antigen pa NK maselo amene amayendetsa cytotoxicity pamene IL15 amapereka kupulumuka ndi kuchuluka zizindikiro ku NK maselo. Mesothelin (MSLN), pakadali pano ndi antigen yotupa yomwe imayang'aniridwa ndi khansa zosiyanasiyana kuphatikiza NSCLC. Kafukufuku wamakono wochitidwa ndi labotale ya Dr. Jeff Miller, University of Minnesota, adayesa ngati TriKE yomwe imayang'aniridwa ndi MSLN ikhoza kuyendetsa cytotoxicity ku maselo a NSCLC pamagulu onse a matenda pamaso pa hypoxia, zovuta mu NSCLC chotupa microenvironment.

Kuphunzira kupanga ndi kusanthula - Kugwiritsa ntchito zotumphukira zamagazi a mononuclear cell (PBMC) omwe amasonkhanitsidwa kuchokera kwa odwala a NSCLC, (1) odwala asanayambe chithandizo chokhazikika, (2) atalandira chithandizo choyambirira komanso (3) pakukula kwa matenda ngati kuli koyenera. Phunzirolo linatsutsa PBMC wodwala ndi NSCLC cell line (NCI-H460) kwa maola 5 pamaso pa monensin ndi brefeldin A, kuyeza degranulation (CD107a) ndi kupanga cytokine (IFNγ) ndi flow cytometry (moyo, CD56 +/ CD3- maselo ). Poyerekeza ndi NK maselo okha (NT); NK maselo okha ndi mankhwala ('TriKE'); kapena NK maselo okhala ndi chotupa chokha.

Results

NSLC asintha ma cell a NK - Kusanthula kosiyanasiyana kwa magawo a chitetezo chamthupi kumayambiriro koyambilira kapena magulu odwala mochedwa adachitidwa pogwiritsa ntchito pulogalamu ya Astrolabe Diagnostics. TriKE adatha kuyambitsa ntchito yayikulu (p <0.0001) motsutsana ndi ma cell a H460 m'magulu onse awiri. Kufufuzaku kunawonetsa kuchuluka kwakukulu kwa maselo a CD56 +/CD16 + NK ndi maselo ochepera a CD33 +/CD14- myeloid odwala oyambirira poyerekeza ndi odwala ochedwa asanayambe chithandizo. Kuperewera kwa CD16, komwe kumayendetsa cytotoxicity, komanso kuchuluka kwa maselo a myeloid, omwe amatha kupondereza ntchito ya NK cell, akuti odwala a NSCLC mochedwa amatha kuyankha mosiyana ndi biologics yolunjika ku NK cell cytotoxicity.

Mesothelin-targeted TriKE imayendetsa NK cell kugwira ntchito mosasamala kanthu za siteji ya matenda komanso magawo onse a chithandizo: Ngakhale hypoxia imawononga NK cell cytotoxicity, TriKE yoyang'aniridwa ndi MSLN yophunzirira inalimbikitsa NK cell cytotoxicity ya maselo a khansa ya m'mapapo (H460) atakumana ndi hypoxia kwa masiku 7. , panthawi yokhudzana ndi hypoxia komanso pakuyesa komweko. Deta inasonyeza kuti TriKE inachititsa kuti degranulation ndi kupanga cytokine mu NK maselo odwala pamaso pa chotupa maselo (H460) pa magawo onse a chithandizo (asanalandire chithandizo, pambuyo mankhwala koyamba ndi pakupita patsogolo).

Kutsiliza - Umboni wodziwikiratu uwu ukusonyeza, ngakhale kusiyana kwa kuzungulira kwa maselo a chitetezo cha mthupi a Stage IVB NSCLC odwala, mesothelin-targeted TriKE akhoza kugwira ntchito limodzi ndi chisamaliro chamakono ndikupereka phindu ngakhale mu hypoxic chilengedwe cha chotupa cholimba.

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Linda Hohnholz

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