Ithemba Elisha Ekwelashweni Komdlavuza: Ukwelashwa kwe-TIL Kuvela Njengomngcele Olandelayo
Insimu yokwelapha ngamaseli iyaqhubeka nokukhula, kanti ukwelashwa kwe-TIL manje kuvela njengentuthuko ebalulekile ku Ukwelashwa KomdlavuzaNaphezu kwamathemba aphezulu abekwe ekwelashweni kwe-CAR-T, umthelela wayo ezimila eziqinile, ezihlanganisa u-90% womdlavuza, ulinganiselwe. Kodwa-ke, ukwelashwa kwe-TIL kukulungele ukushintsha leyo ndaba.
Ukwelashwa kwe-TIL muva nje kuthole ukunakwa okukhulu lapho i-Lifileucel ka-Iovance Biotherapeutics ithola ukuvunyelwa kwe-FDA okusheshayo ngomhlaka-16 kuNhlolanja kokwelashwa kwe-melanoma eye yathuthuka ngemuva kokwelashwa kwe-PD-1 antibody. Ukuvunyelwa kwe-Lifileucel kuyiphawula njengokwelashwa kokuqala kwe-TIL ukufika emakethe, okubonisa isigaba esisha ekwelashweni kwamaseli okugxile ezimila eziqinile.
Indlela Ende Eya Empumelelweni
Uhambo lokwelashwa kwe-TIL luthatha iminyaka engaphezu kwamashumi amane. Ama-Lymphocyte Angena Esimila (ama-TIL) ayiqembu elihlukahlukene lamaseli omzimba atholakala ngaphakathi kwe-microenvironment yesimila, okuhlanganisa amaseli e-T, amaseli e-B, Iseli le-Nks, ama-macrophage, kanye namaseli okucindezela atholakala ku-myeloid. Lawa maseli, avame ukulinganiselwa ngenani kanye nomsebenzi ngaphakathi kwezimila, angavunwa, anwetshwe elebhu, futhi aphinde afakwe esigulini ukuze aqondise futhi abhubhise amaseli omdlavuza.
Ngokungafani namaseli e-CAR-T, ama-TIL atholakala ngqo esimila, okuwavumela ukuthi abone uhla olubanzi lwama-antigen esimila futhi anikeze amaphrofayili angcono okungena kanye nokuphepha. Le ndlela ibonise ithemba, ikakhulukazi ekwelapheni izimila eziqinile lapho i-CAR-T ibilokhu ilwela khona ukwenza intuthuko.
Ukunqoba Izinselele
I-Lifileucel ibonise imiphumela emihle kakhulu yezokwelapha, inikeza ithemba ezigulini ze-melanoma ezinezinketho zokwelapha ezilinganiselwe. Esivivinyweni sezokwelapha se-C-144-01, ukwelashwa kufinyelele izinga lokuphendula eliqondile elingu-31%, kanti iziguli ezingu-42% zithola izimpendulo ezihlala iminyaka engaphezu kwemibili. Naphezu kwalezi mpumelelo, indlela eya ekuthathweni kabanzi ibhekene nezingqinamba ezinkulu.
Izinselele Zezimboni Nezentengiselwano
Enye yezinselele eziyinhloko uhlobo lomuntu ngamunye Umkhiqizo we-Tili-ion, edinga inqubo yokukhiqiza ende neyinkimbinkimbi. Nakuba i-Iovance inciphise isikhathi sokukhiqiza saba cishe yizinsuku ezingu-22, kudingeka ukusheshisa okwengeziwe ukuze kuhlangatshezwane nezidingo zesiguli ngokushesha. Le nkampani ihlose ukufinyeza lesi sikhathi sibe yizinsuku ezingu-16 ngokuqhubeka nokuthuthukiswa.
Ukuhweba nakho kuletha izithiyo. Izindleko eziphakeme zokwelapha komuntu siqu—okwamanje ezibiza u-$515,000 we-Lifileucel, kanye nezindleko ezengeziwe zokwelapha—zikhawulela ukwamukelwa kusenesikhathi emakethe yase-US. Ukuze kufinyelelwe ukufinyelela emhlabeni wonke kanye nokusebenza kahle kwezomnotho, izinkampani kumele zenze lula ukukhiqiza futhi zinciphise izindleko.
Ukwenza lula inqubo yokwelapha ukuze kuthuthukiswe ulwazi lwesiguli kungenye into ebalulekile. Ukwelashwa kwe-TIL kuhilela izinyathelo eziningi, okuhlanganisa ukuqoqwa kwezicubu zesimila, ukukhuliswa kwamaseli, kanye nokususwa kwama-lymphocyte, konke kudinga izikhungo zezokwelapha ezikhethekile kanye nabasebenzi. Ukwakha inethiwekhi yokwelapha ebanzi nephumelelayo kubalulekile empumelelweni ebanzi yezentengiselwano.
Ikusasa Lesithembiso
Uma sibheka phambili, ukwanda kokwelashwa kwe-TIL kwezinye izimila eziqinile kusalokhu kuyinjongo ebalulekile. Ngenkathi ucwaningo lwamanje lugxile kakhulu kwi-melanoma, kuyaqhubeka imizamo yokuhlola ukusebenza kwayo kwezinye izinhlobo zomdlavuza ezifana nomdlavuza wamaphaphu ongewona amaseli amancane. Ukuqonda izici zokwelashwa kwe-TIL, okuhlanganisa ukuhlonza ukuthi yimaphi amaseli e-T asebenza kahle kakhulu nokuthuthukisa ukwelashwa okuhlanganisiwe, kuzobaluleka kakhulu.
Izindlela zokwelapha ezihlanganisiwe, ezihlanganisa ama-TIL nokwelashwa okuvamile njengokwelashwa ngamakhemikhali, imisebe, ama-immunotherapy, kanye nemijovo, zibonisa amandla okuthuthukisa imiphumela yokwelashwa kanye nokunciphisa imiphumela emibi. Izinkampani ezifana ne-Iovance sezivele zihlola ukuhlanganiswa nama-PD-1 inhibitors, zihlose ukuthuthukisa ukusebenza kahle kwe-TIL kanye namazinga okusabela kweziguli.
Njengoba i-Lifileucel ivula indlela yokwelashwa kwe-TIL, insimu yokwelashwa kwamaseli imi onqenqemeni lwenkathi yokuguqula ekwelashweni kwesimila esiqinile. Imizamo ehlangene kanye nokusungula izinto ezintsha okuvela ezinkampanini zemithi kuzonquma ukuthi ubani ohola lo mngcele omusha. Ithemba elivuselelwe ukwelashwa kwe-TIL lithembisa ukudonsa izinsiza ezengeziwe kanye nokunaka, liqhube intuthuko futhi linikeze ithemba elisha ezigulini emhlabeni jikelele.