Imiphumela iphakamisa ukuthi i-TriKE ehloselwe i-mesothelin ingasebenza ngokuhambisana nezinga lamanje lokunakekela futhi inikeze inzuzo ngisho nasendaweni ene-hypoxic yesimila esiqinile.
I-GT Biopharma, Inc., inkampani yesigaba somtholampilo ye-immuno-oncology egxile ekuthuthukiseni izindlela zokwelapha ezintsha ezisuselwe ekuhlanganyeleni kwamaseli eNkampani e-tri-specific tri-specific natural killer (NK), iplatifomu ye-TriKE® protein biologic technology, yethule idatha ye-preclinical ebonisa inoveli yayo i-TriKE ishayela i-NK. cell immunotherapy ngokumelene nomdlavuza wamaphaphu ongewona omncane (NSCLC) ku-hypoxic solid tumor microenvironment ku-ESMO's Targeted Anticancer Therapies Congress (TAT).
UGregory Berk, MD, uMongameli weNkampani we-R&D kanye neSikhulu Esiphezulu Sezokwelapha waphawula, “Lobu bufakazi bangaphambi komtholampilo buphakamisa, naphezu komehluko ekujikelezeni kwamaseli omzimba eziguli ze-Stage IVB NSCLC, i-TriKE ehloselwe i-mesothelin ingasebenza ngokuhambisana nezinga lamanje lokunakekelwa futhi inikeze inzuzo ngisho nasendaweni ye-hypoxic yesimila esiqinile, okudinga uphenyo olwengeziwe lwale noveli, i-TriKE ehlosiwe. "
Ukushayela i-NK cell immunotherapy ngokumelene ne-NSCLC, kumongo we-hypoxia, usebenzisa i-Tri-specific Killer Engager (TriKE®)
Isendlalelo - Okwamanje, ababulali abakhethekile abathathu (i-TriKE®) bayahlolwa emtholampilo ukuze belaphe i-leukemia ne-lymphoma. Le CD16/FcγRIII ye-TriKE's cross-link kanye ne-antigen yesimila kumaseli e-NK aqhuba i-cytotoxicity kuyilapho i-IL15 inikeza amasignali okusinda nokusabalala kumaseli e-NK. I-Mesothelin (MSLN), njengamanje iyi-antigen yesimila eqondiswe kumdlavuza ohlukahlukene kubandakanya i-NSCLC. Ucwaningo lwamanje olwenziwa ilabhorethri kaDkt. Jeff Miller, iNyuvesi yaseMinnesota, luhlole ukuthi i-TriKE ehloselwe i-MSLN ingakwazi yini ukushayela i-cytotoxicity kumaseli e-NSCLC kuzo zonke izigaba zesifo lapho kukhona i-hypoxia, inselele ku-NSCLC tumor microenvironment.
Idizayini yokufunda nokuhlaziya - Ukusebenzisa i-peripheral blood mononuclear cells (PBMC) eqoqwe ezigulini ze-NSCLC, (1) ngaphambi kokuba iziguli ziqale ukwelashwa okujwayelekile, (2) ngemva kokwelashwa kokuqala kanye (3) ekuqhubekeleni phambili kwesifo lapho kufanele khona. Ucwaningo luphonsele inselele i-PBMC yesiguli nge-NSCLC cell line (NCI-H460) amahora angu-5 phambi kwe-monensin ne-brefeldin A, i-degranulation yokulinganisa (CD107a) nokukhiqizwa kwe-cytokine (IFNγ) nge-flow cytometry (bukhoma, i-CD56 +/CD3- cell eyodwa ). Uma kuqhathaniswa namaseli e-NK kuphela (NT); Amaseli e-NK ewodwa anesidakamizwa ('TriKE'); noma amaseli e-NK anethumba lodwa.
Imiphumela
I-NSLC iguqule amaseli e-NK - Ukuhlaziywa kobuningi okuhlukile kwamasethi amasosha omzimba esigabeni sokuqala noma amaqembu eziguli asesiteji sakamuva kwenziwa kusetshenziswa isoftware ye-Astrolabe Diagnostics. I-TriKE ikwazile ukuheha umsebenzi obalulekile (p<0.0001) ngokumelene namaseli e-H460 kuwo womabili amaqembu. Ukuhlaziywa kwembula inqwaba yamaseli e-CD56+/CD16+ NK kanye namaseli e-CD33+/CD14- myeloid ambalwa ezigulini ezisakhula uma kuqhathaniswa neziguli ezisesigabeni sekwephuzile ngaphambi kokuqala kokwelashwa. Ukuntuleka kwe-CD16, eqhuba i-cytotoxicity, kanye nobuningi bamaseli e-myeloid, angacindezela ukusebenza kwe-NK cell, kusikisela ukuthi iziguli ze-NSCLC zesigaba sekwephuzile zingasabela ngendlela ehlukile ku-biologics eqondise i-NK cell cytotoxicity.
I-TriKE ehloselwe i-Mesothelin ishayela i-NK cell ukusebenza kungakhathaliseki ukuthi yisiphi isigaba sesifo nakuzo zonke izigaba zokwelashwa: Nakuba i-hypoxia ikhubaza i-NK cell cytotoxicity, i-TriKE ehloselwe i-MSLN yocwaningo ithuthukise i-NK cell cytotoxicity yamaseli omdlavuza wamaphaphu (H460) ngemva kokuchayeka ku-hypoxia izinsuku ezingu-7. , ngesikhathi sokuchayeka ku-hypoxia kanye nokuhlolwa ngokwayo. Idatha yabonisa ukuthi i-TriKE ibangele ukuwohloka kwe-degranulation kanye nokukhiqizwa kwe-cytokine kumaseli e-NK esiguli lapho kukhona amaseli wesimila (H460) kuzo zonke izigaba zokwelashwa (ngaphambi kokwelashwa, ngemva kokwelashwa kokuqala kanye nokuqhubeka).
Isiphetho - Lobu bufakazi bangaphambi komtholampilo buphakamisa, naphezu komehluko ekujikelezeni kwamangqamuzana omzimba omzimba ezigulini ze-Stage IVB NSCLC, i-mesothelin-targeted TriKE ingasebenza ngokuhambisana nezinga lamanje lokunakekelwa futhi inikeze inzuzo ngisho nasendaweni ye-hypoxic yesimila esiqinile.
LOKHO ONGAKUTHATHE KULESI SIHLOKO:
- , 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).
