Iziphumo zibonisa ukuba i-mesothelin ejoliswe kuyo i-TriKE inokusebenza ecaleni komgangatho wangoku wokhathalelo kwaye ibonelele ngenzuzo nakwimekobume ye-hypoxic yethumba elomeleleyo.
I-GT Biopharma, Inc., inqanaba lezonyango inkampani ye-immuno-oncology egxile ekuphuhliseni unyango olutsha olusekwe kumbulali wendalo weNkampani ongumnini we-tri-specific (NK) weseli, iqonga letekhnoloji ye-TriKE® ye-protein ye-biologic, ibonise idatha ye-preclinical ebonisa inoveli yayo i-TriKE eqhuba i-NK. iseli immunotherapy ngokuchasene nomhlaza wemiphunga yeseli engeyincinci (NSCLC) kwi-hypoxic solid tumor microenvironment kwi-ESMO's Targeted Anticancer Therapies Congress (TAT).
UGregory Berk, MD, uMongameli weNkampani ye-R&D kunye neGosa eliyiNtloko lezoNyango uthe, "Obu bungqina bangaphambili bubonisa, nangona umahluko wokujikeleza iiseli ze-immune ze-Stage IVB NSCLC izigulana, i-TriKE ejoliswe kwi-mesothelin inokusebenza kunye nomgangatho wangoku wokhathalelo kwaye Ukubonelela ngenzuzo nakwimeko ye-hypoxic yethumba eliqinileyo, elifanele uphando olongezelelweyo lwale noveli, ekujoliswe kuyo kwi-TriKE. "
Ukuqhuba i-NK cell immunotherapy ngokuchasene ne-NSCLC, kumxholo we-hypoxia, usebenzisa i-Tri-specific Killer Engager (TriKE®)
Imvelaphi - Okwangoku, ababulali be-Tri-specific (TriKE®) bayavavanywa kwikliniki ukunyanga i-leukemia kunye ne-lymphoma. Le TriKE kaThixo cross-link CD16/FcγRIII kunye nethumba antigen kwiiseli NK leyo eqhuba cytotoxicity ngelixa IL15 ibonelela ukusinda kunye nemiqondiso nokwanda kwiiseli NK. I-Mesothelin (MSLN), okwangoku i-antigen ye-tumor ekujoliswe kuyo kwiintlobo zomhlaza ezahlukeneyo kuquka i-NSCLC. Uphononongo lwangoku olwenziwa nguDkt. Jeff Miller's laboratory, iYunivesithi yaseMinnesota, ivavanye ukuba i-TriKE ejoliswe kwi-MSLN inokuqhuba i-cytotoxicity kwiiseli ze-NSCLC kuzo zonke izigaba zesifo phambi kwe-hypoxia, umngeni kwi-NSCLC tumor microenvironment.
Uyilo lwesifundo kunye nohlalutyo - Ukusebenzisa i-peripheral blood mononuclear cells (PBMC) eqokelelwe kwizigulane ze-NSCLC, (1) ngaphambi kokuba izigulane ziqale unyango oluqhelekileyo, (2) emva konyango lokuqala kunye (3) nokuqhubela phambili kwesifo apho kuyimfuneko. Uphononongo lucelomngeni i-PBMC yesigulane kunye ne-NSCLC cell line (NCI-H460) kwiiyure ze-5 phambi kwe-monensin kunye ne-brefeldin A, ukulinganisa i-degranulation (CD107a) kunye nokuveliswa kwe-cytokine (IFNγ) nge-flow cytometry (iphila, i-CD56 + / CD3- iiseli ). Xa kuthelekiswa neeseli ze-NK zodwa (NT); Iiseli ze-NK zizodwa ezinechiza ('TriKE'); okanye iiseli ze-NK ezinethumba lodwa.
iziphumo
I-NSLC iguqule iiseli ze-NK - Uhlalutyo oluninzi oluhlukeneyo lwe-immune subsets kwinqanaba lokuqala okanye amaqela ezigulane zasemva kwexesha ayenziwa ngokusebenzisa i-software ye-Astrolabe Diagnostics. I-TriKE yakwazi ukwenza umsebenzi obalulekileyo (p <0.0001) ngokuchasene neeseli ze-H460 zombini amaqela. Uhlalutyo lubonise ubuninzi obukhulu beeseli ze-CD56 +/CD16+ NK kunye neeseli ze-CD33 +/CD14- myeloid ezimbalwa kwizigulane zesigaba sokuqala xa kuthelekiswa nezigulane zasemva kwexesha ngaphambi kokuba kuqale unyango. Ukungabikho kwe-CD16, eqhuba i-cytotoxicity, kunye nobuninzi beeseli ze-myeloid, ezinokucinezela ukusebenza kweeseli ze-NK, kucetyiswa ukuba izigulane ze-NSCLC zasemva kwexesha zingaphendula ngokwahlukileyo kwi-biologics ejolise kwi-NK cell cytotoxicity.
I-TriKE ejoliswe kwi-Mesothelin iqhuba ukusebenza kweeseli ze-NK kungakhathaliseki ukuba liliphi na inqanaba lesifo nakuwo onke amanqanaba onyango: Ngelixa i-hypoxia iphazamisa i-NK cell cytotoxicity, i-TriKE ejoliswe kwi-MSLN yophononongo iphucule i-NK cell cytotoxicity yeeseli zomhlaza wemiphunga (H460) emva kokuba sesichengeni se-hypoxia iintsuku ezisi-7. , ngexesha lokuvezwa kwi-hypoxia kunye nakwi-assay ngokwayo. Idatha ibonise ukuba i-TriKE yenza ukuba i-degranulation ibangele kunye nokuveliswa kwe-cytokine kwiiseli ze-NK zesigulana xa kukho iiseli ze-tumor (H460) kuzo zonke izigaba zonyango (ngaphambi konyango, emva konyango lokuqala kunye nokuqhubeka).
Isiphelo - Obu bungqina bangaphambi kweklinikhi bubonisa, nangona kukho umahluko ekujikelezeni kweeseli ze-immune ze-Stage IVB NSCLC izigulane, i-mesothelin ejoliswe kuyo i-TriKE inokusebenza kunye nomgangatho wangoku wokunyamekela kwaye ibonelele ngenzuzo nakwimeko ye-hypoxic ye-tumor eqinile.
INTO ONOKUYITHATHA KWELI NQAKU:
- , the Company’s President of R&D and Chief Medical Officer noted, “This pre-clinical evidence suggests, despite the difference in circulating immune cells of Stage IVB NSCLC patients, a mesothelin-targeted TriKE can work alongside current standard of care and provide benefit even in the hypoxic environment of a solid tumor, meriting further investigation of this novel, targeted TriKE.
- Jeff Miller’s laboratory, University of Minnesota, evaluated whether a MSLN-targeted TriKE could drive cytotoxicity towards NSCLC cells at all stages of disease in the presence of hypoxia, a challenge in the NSCLC tumor microenvironment.
- The data demonstrated that TriKE induced degranulation and cytokine production in patient NK cells when in the presence of tumor cells (H460) at all stages of treatment (before treatment, after initial treatment and at progression).
