Tobetsa mona ho bonts'a lifolakha tsa HAO leqepheng lena mme u lefelle katleho feela

Litaba tsa mohala

Kankere e sa Nyane ea Matšoafo ea Lisele: Lintlha tse Ncha tsa Preclinical

ngotsoeng ke mohlophisi

Liphetho li fana ka maikutlo a hore mesothelin-targed TriKE e ka sebetsa hammoho le maemo a hajoale a tlhokomelo mme ea fana ka molemo le tikolohong ea hypoxic ea hlahala e tiileng.

GT Biopharma, Inc., k'hamphani ea kliniki ea immuno-oncology e tsepamisitseng maikutlo ho nts'etsopele ea mekhoa e mecha ea kalafo e ipapisitseng le ts'ebeliso ea lisele tsa K'hamphani ea "tri-specific natural killer" (NK), sethala sa theknoloji ea protheine ea TriKE®, e hlahisitse lintlha tsa pele tse bonts'ang buka ea eona ea TriKE ho khanna NK. cell immunotherapy khahlano le mofetše o seng o monyane oa lisele tsa matšoafo (NSCLC) sebakeng sa hypoxic solid tumor microenvironment ho ESMO's Targeted Anticancer Therapies Congress (TAT).

Gregory Berk, MD, Mopresidente oa Khampani oa R&D le Ofisiri e ka Sehloohong ea Bongaka o hlokometse, "Bopaki bona ba pele ho tleliniki bo fana ka maikutlo a hore, leha ho na le phapang ea ho potoloha ha lisele tsa 'mele tsa Stage IVB NSCLC, TriKE e lebisitsoeng ho mesothelin e ka sebetsa hammoho le maemo a hajoale a tlhokomelo. e fana ka melemo leha e le tikolohong ea hypoxic ea hlahala e tiileng, e hlokang lipatlisiso tse ling tsa buka ena, e lebisitsoeng ho TriKE. ”

Ho khanna NK cell immunotherapy khahlanong le NSCLC, maemong a hypoxia, ho sebelisa Tri-specific Killer Engager (TriKE®)

Background - Hajoale, batho ba etsang liteko tsa Tri-specific killer (TriKE®) ba ntse ba etsa liteko tleliniking ho phekola leukemia le lymphoma. TriKE's cross-link CD16/FcγRIII le antigen ea tumor ho NK cell e tsamaisang cytotoxicity ha IL15 e fana ka matšoao a ho pholoha le ho ata ho NK liseleng. Mesothelin (MSLN), hajoale ke antigen ea tumor e lebisitsoeng ho mefuta e fapaneng ea mofetše ho kenyeletsoa NSCLC. Phuputso ea morao-rao e entsoeng ke laboratori ea Dr. Jeff Miller, Univesithi ea Minnesota, e ile ea hlahloba hore na TriKE e lebisitsoeng ke MSLN e ka khanna cytotoxicity ho ea lisele tsa NSCLC likarolong tsohle tsa lefu ka pel'a hypoxia, phephetso ho NSCLC tumor microenvironment.

Sebopeho sa thuto le tlhahlobo - Ho sebelisa lisele tsa peripheral blood mononuclear cell (PBMC) tse bokelitsoeng ho bakuli ba NSCLC, (1) pele bakuli ba qala phekolo e tloaelehileng, (2) ka mor'a phekolo ea pele le (3) tsoelo-pele ea mafu moo ho hlokahalang. Phuputso e ile ea phephetsa PBMC ea mokuli ka mohala oa sele ea NSCLC (NCI-H460) bakeng sa lihora tsa 5 ka pel'a monensin le brefeldin A, ho lekanya degranulation (CD107a) le tlhahiso ea cytokine (IFNγ) ka phallo cytometry (phela, CD56 +/ CD3- lisele ). Ha ho bapisoa le lisele tsa NK feela (NT); NK lisele tse le mong le lithethefatsi ('TriKE'); kapa NK lisele tse nang le hlahala feela.

Results

NSLC e fetotse lisele tsa NK - Tlhahlobo e fapaneng ea bongata ba li-immune subsets qalong kapa lihlopha tsa bakuli tsa morao-rao li ile tsa etsoa ho sebelisoa software ea Astrolabe Diagnostics. TriKE e ile ea khona ho kenya ts'ebetso ea bohlokoa (p <0.0001) khahlanong le lisele tsa H460 bakeng sa lihlopha ka bobeli. Tlhahlobo e ile ea senola bongata bo boholo ba lisele tsa CD56 +/CD16 + NK le lisele tse fokolang tsa CD33 +/CD14- myeloid ho bakuli ba pele ba ho bapisoa le bakuli ba morao-rao pele phekolo e qala. Ho haella ha CD16, e tsamaisang cytotoxicity, le bongata ba lisele tsa myeloid, tse ka hatellang ts'ebetso ea lisele tsa NK, ho khothalelitse bakuli ba NSCLC ba morao-rao ba ka arabela ka tsela e fapaneng ho biologics e shebaneng le NK cell cytotoxicity.

Mesothelin-targeted TriKE e khanna NK cell function ho sa tsotelehe boemo ba lefu le mekhahlelo eohle ea kalafo: Le hoja hypoxia e sitisa NK cell cytotoxicity, thuto ea MSLN-targeted TriKE e ntlafatsa NK cell cytotoxicity ea lisele tsa kankere ea matšoafo (H460) ka mor'a ho ba le hypoxia ka matsatsi a 7. , nakong ea ho pepesehela hypoxia le tekong ka boeona. Lintlha li bontšitse hore TriKE e entse hore ho be le degranulation le tlhahiso ea cytokine liseleng tsa NK tsa mokuli ha ho na le lisele tsa hlahala (H460) ka mekhahlelo eohle ea phekolo (pele ho phekolo, ka mor'a phekolo ea pele le tsoelo-pele).

Qetello - Bopaki bona ba pele ho kliniki bo fana ka maikutlo, ho sa tsotellehe phapang ea ho potoloha lisele tsa 'mele tsa ho itšireletsa mafung tsa Stage IVB NSCLC bakuli, mesothelin-targeted TriKE e ka sebetsa hammoho le maemo a hona joale a tlhokomelo le ho fana ka molemo esita le tikolohong ea hypoxic ea hlahala e tiileng.

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mohlophisi

Mohlophisi e moholo oa eTurboNew ke Linda Hohnholz. O lula ntlong e kholo ea eTN e Honolulu, Hawaii.

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