I-Oncolytics Biotech® Inc. namuhla imemezele ukushicilelwa kwedatha ye-preclinical ebonisa umsebenzi we-synergistic wokulwa nomdlavuza we-pelareorep ohlanganiswe ne-chimeric antigen receptor (CAR) T cell therapy kumathumba aqinile. Leli phepha, elinesihloko esithi "Ukunwetshwa kwe-Oncolytic virus-mediated of dual-Specific CAR T cell kuthuthukisa ukusebenza kahle ngokumelene nezimila eziqinile kumagundane," lanyatheliswa ku-Science Translational Medicine ngokubambisana nabacwaningi bezikhungo eziningana ezihlonishwayo, okuhlanganisa iMayo Clinic kanye neDuke University. Isixhumanisi sephepha singatholakala ngokuchofoza lapha.
"Ukuba le miphumela ishicilelwe kujenali enethonya eliphezulu kunikeza ukuqinisekiswa okubalulekile kwangaphandle kokubaluleka kwayo," kusho uThomas Heineman, MD, Ph.D., Isikhulu Esiphezulu Sezokwelapha se-Oncolytics Biotech Inc. "Ngenkathi amaseli e-CAR T ekhiqize isikhathi eside. ukwelapha ezinkingeni ze-hematological1, i-immunosuppressive tumor microenvironments (TMEs) yomdlavuza wezitho eziqinile kuze kube manje inciphise ukusebenza kwayo kulezi zinkomba. I-Pelareorep iye yaboniswa kaningi ukuthi ihlehlisa ama-TME avikelayo, futhi ekushicilelweni kwamanje i-pelareorep iboniswa ukunika amandla ukusebenza kwamaseli e-CAR T kumamodeli amaningi we-murine aqinile we-tumor. Lokhu ukuthola okunamandla okuthi, uma kuhunyushwa emtholampilo, kungathuthukisa kakhulu ukubikezelwa kweziguli ezinomdlavuza odlange kakhulu ngokunikeza inoveli kanye nenketho yokwelapha ehlala isikhathi eside. Ngokubonisa ikhono lokuthuthukisa ukukhuthazela kwe-T cell, ukunciphisa ukuphunyuka kwe-antigen, futhi kunqobe ama-TME aqinile aqinile, ukufakwa kwe-pelareorep kubhekana nezithiyo ezintathu eziyinselele kakhulu zokwelashwa okuphumelelayo kwe-CAR T. "
U-Andrew de Guttadauro, uMongameli we-Oncolytics Biotech US kanye neNhloko Yomhlaba Wonke Yezokuthuthukiswa Kwebhizinisi, wengeza, “Naphezu kokushintsha indlela yokwelapha umdlavuza othile kanye nokudayiswa kwezigidigidi zamarandi ngonyaka odlule, imishanguzo ye-CAR T okwamanje isiza iziguli ezincane eziphethwe i-hematological. izifo ezimbi. Ngale miphumela yakamuva, manje sesinobufakazi obuqinile bokuthi i-pelareorep ingalivula ngokugcwele inani lezindlela zokwelapha ze-CAR T ngokwandisa amandla azo okuhweba emakethe enkulu kakhulu yeziguli ezinomdlavuza ezilwa nezimila eziqinile.”
Izifundo ze-preclinical ezishicilelwe ephepheni zahlola ukuphikelela nokusebenza kahle kwamaseli e-CAR T alayishwe i-pelareorep ("ukwelashwa kwe-CAR/Pela") kumamodeli amaningi e-murine eqinile yesimila. Imiphumela yokuhlanganisa ukwelapha kwe-CAR/Pela nedosi ye-intravenous eyalandela ye-pelareorep (“pelareorep boost”) nayo yaphenywa. Idatha eyinhloko neziphetho ezivela ephepheni zihlanganisa:
• Ukuphikelela nomsebenzi wokulwa nomdlavuza wamaseli e-CAR T ube ngcono kakhulu uma elayishwe i-pelareorep. Uma kuqhathaniswa nanoma yikuphi ukwelashwa kuphela, ukwelashwa ngokwelashwa kwe-CAR/Pela kuholele ezinzuzweni ezibalulekile ngokwezibalo esikhumbeni se-murine namamodeli omdlavuza wobuchopho.
• Ukwelashwa kwe-CAR/Pela okulandelwa i-pelareorep boost kuholele ekusebenzeni okuthuthukisiwe esikhumbeni se-murine namamodeli omdlavuza wobuchopho kanye nokwelapha isimila ku->80% wamagundane alashiwe kumodeli ngayinye.
• Ukulayisha amaseli e-CAR T nge-pelareoep kuholele ekuqondisweni kweseli lomdlavuza okuthuthukisiwe futhi kwavimbela ukuphunyuka kwe-antigen ku-vivo ngokukhiqiza amaseli e-CAR T anokucaciswa okukabili aqondise i-antigen yawo eklanyelwe kanye ne-antigen yomdabu ye-T cell receptor. Le miphumela ibonisa ukuthi ukwelashwa kwe-CAR/Pela kungase kunikeze izinzuzo zokwelapha ezihlala isikhathi eside uma kuqhathaniswa nokwelashwa ngamaseli e-CAR T kuphela.
UDkt. Matt Coffey, uMongameli kanye neSikhulu Esiphezulu se-Oncolytics Biotech Inc. kanye nombhali wephepha baphawule, “Le miphumela ethokozisayo iyisibonelo esihle kakhulu sendlela esisebenzisa ngayo ubudlelwano nabaholi bemibono esemqoka kanye nezikhungo zocwaningo eziphambili ukuze sandise amandla e-pelareorep. umthelela wokwelapha. Lokhu kusivumela ukuthi sihlale sigxile kakhulu ohlelweni lwethu lomdlavuza webele ohamba phambili, olubonise ukuthi ikhono le-pelareorep lokukhuthaza ukungena kwe-tumor T cell liholela ekusebenzisaneni nama-checkpoint inhibitors emtholampilo. Lokhu okutholakele okusanda kushicilelwa kwangaphambi komtholampilo kubonisa izinzuzo ze-pelareorep ze-synergistic zidlulela nangaphezu kwama-checkpoint inhibitors futhi zigqamisa ithuba lokwandisa isibalo sethu seziguli esingalungiseka. Njengoba siphishekela leli thuba siya phambili, sihlose ukusebenzisa ubudlelwano nabalingani bezemfundo noma basembonini ukuze siqhubeke sisebenzisa izinjongo zethu zomtholampilo nezebhizinisi ngempumelelo. "
LOKHO ONGAKUTHATHE KULESI SIHLOKO:
- Pelareorep has repeatedly been shown to reverse immunosuppressive TMEs, and in the present publication pelareorep is shown to enable the effectiveness of CAR T cells in multiple murine solid tumor models.
- Loading CAR T cells with pelareoep led to improved cancer cell targeting and prevented antigen escape in vivo by generating CAR T cells with dual specificity that target their designed antigen and the native T cell receptor antigen.
- By demonstrating the ability to improve T cell perseverance, reduce antigen escape, and overcome challenging solid tumor TMEs, the inclusion of pelareorep addresses the three most challenging roadblocks to effective CAR T therapy.
