Iyini i-cancer immunotherapy?

I-Immunotherapy yilapho izingxenye zamasosha omzimba womuntu ogulayo zisetshenziselwa ukulwa nezifo nokutheleleka, kulokhu umdlavuza. Lokhu kwenziwa ngokugqugquzela amasosha omzimba ukuthi asebenze ngokuzikhandla, noma ngokunikeza izakhi zamasosha omzimba ukulwa nesifo noma ukutheleleka.

Udokotela uWilliam Coley wathola ukuthi ukutheleleka ngemva kokuhlinzwa kubonakala kusiza ezinye iziguli ezinomdlavuza. Kamuva wazama ukwelapha iziguli ezinomdlavuza ngokuzithelela ngamagciwane. Lesi yisisekelo se-immunotherapy yesimanje, nakuba manje singatheleli iziguli; sivula amasosha abo omzimba sisebenzisa izindlela ezahlukahlukene noma sinikeze amasosha abo omzimba amathuluzi okulwa nawo.

Ezinye izinhlobo ze-immunotherapy zomdlavuza zithuthukisa amasosha omzimba ewonke, kanti ezinye zisebenzisa amasosha omzimba ukuhlasela amangqamuzana omdlavuza ngokuqondile. Abacwaningi bakwazile ukuthola indlela yokuthola amasosha omzimba womuntu ukuze abone amangqamuzana omdlavuza emzimbeni futhi aqinise impendulo yawo.

Kunezinhlobo ezintathu ze-immunotherapy yomdlavuza: amasosha omzimba e-monoclonal, imigomo yomdlavuza, kanye ne-non-specific immunotherapy's. Iqhinga nge-cancer immunotherapy ukuthola ukuthi yimaphi ama-antigen akuseli lomdlavuza, noma yimaphi ama-antigen abandakanyeka kumdlavuza noma amasosha omzimba.

Izinhlobo ze-Immunotherapy kanye Nezicelo Zazo Zomdlavuza

Amasosha omzimba e-Monoclonal enziwa umuntu noma akhiwe ngamangqamuzana egazi amhlophe esiguli, futhi asetshenziselwa ukukhomba amasosha omzimba noma amasosha omzimba athile kumaseli omdlavuza.

Isinyathelo sokuqala sokwenza amasosha omzimba e-monoclonal ukukhomba i-antigen efanele ukuhloswa ngayo. Lokhu kunzima ngomdlavuza njengoba kunama-antigen amaningi ahilelekile. Amanye ama-cancer ayakwazi ukumelana ne-monoclonal antibodies kunezinye kodwa, njengoba ama-antigen amaningi exhunywe ezinhlotsheni ezithile zomdlavuza, amasosha omzimba we-monoclonal asebenza kakhulu.

Kunezinhlobo ezimbili ze-monoclonal antibodies; eyokuqala yi-conjugated monoclonal antibodies. Lezi zinezinhlayiya ezikhipha imisebe noma imithi yokwelapha ngamakhemikhali exhunywe kumasosha omzimba. I-antibody icinga futhi inamathele engqamuzaneni yomdlavuza lapho umuthi noma izinhlayiyana zinganikezwa khona ngokuqondile. Lokhu kwelashwa akuyingozi kangako kunendlela evamile ye-chemo noma yokwelapha ngemisebe.

Uhlobo lwesibili amasosha omzimba anqunu we-monoclonal futhi, njengoba igama libonisa, lawa awanawo umuthi we-chemotherapy noma izinto ezikhipha imisebe enamathiselwe kuwo. Lolu hlobo lwama-antibody lusebenza ngokwalo, nakuba lusanamathela kuma-antigen kumaseli omdlavuza kanye namanye amangqamuzana angenawo umdlavuza noma amaprotheni antantayo amahhala.

Ezinye zithuthukisa ukusabela komzimba ngokusebenza njengomaka wama-T-cell lapho enamathiselwe kumaseli omdlavuza. Abanye baqinisa isimiso somzimba sokuzivikela ezifweni sisonke ngokugxila ezindaweni zokuhlola amasosha omzimba. Isibonelo samasosha omzimba anqunu we-monoclonal (NmAbs) umuthi othi "Alemtuzumab" owenziwe yiCampath. I-Alemtuzumab isetshenziselwa iziguli ezine-chronic lymphocytic leukemia (CLL). Amasosha omzimba aqondise kuma-CD52 antigen kuma-lymphocyte, okuhlanganisa namaseli e-leukemia, futhi ahehe amaseli omzimba eziguli ukuthi abhubhise amangqamuzana omdlavuza.

Imithi yokugomela umdlavuza, enye indlela ye-monoclonal antibody, iqondise ekuphenduleni kwamasosha omzimba kuma-virus kanye nezifo ezingaholela kumdlavuza. Ngokusebenzisa izimiso ezifanayo zomgomo ovamile, okugxilwe kakhulu emithini yokugoma umdlavuza ukusebenza njengesinyathelo sokuvimbela ngaphezu kwesilinganiso sokwelapha.Imithi yokugomela umdlavuza ayiwahlaseli ngokuqondile amangqamuzana omdlavuza.

Imithi yokugomela umdlavuza isebenza ngokufana nemithi yokugoma ejwayelekile ngendlela evuselela ngayo amasosha omzimba, nokho ngomgomo womdlavuza amasosha omzimba aqondiswe ekuhlaseleni amaseli omdlavuza adalwa igciwane kunegciwane ngokwalo.

Kuyaziwa ukuthi ezinye izinhlobo ze-human papilloma virus (HPV) zixhumene nomdlavuza womlomo wesibeletho, wendunu, womphimbo kanye neminye. Ukwengeza, abantu abane-hepatitis B (HBV) engapheli basengozini enkulu yokuthola umdlavuza wesibindi.

Kwesinye isikhathi, ukwakha umuthi wokugomela i-HPV, isibonelo, isiguli esitheleleke ngegciwane le-human papilloma sizokhishwa isampula yamaseli amhlophe egazi. Lawa mangqamuzana azovezwa ezintweni ezithile okuthi, lapho ebuyiselwa kumasosha omzimba esiguli, azodala impendulo ekhulayo yokuzivikela komzimba. Umuthi wokugoma owenziwe ngale ndlela uzoba ngqo kumuntu amangqamuzana amhlophe egazi athathwa kuye. Lokhu kungenxa yokuthi amangqamuzana egazi amhlophe azofakwa ikhodi nge-DNA yomuntu evumela ukuthi umgomo uhlanganiswe ngokugcwele namasosha omzimba.

I-immunotherapy yomdlavuza engaqondile ayiqondi ngqo kumaseli omdlavuza kodwa ivuselela amasosha omzimba wonke. Lolu hlobo lwe-immunotherapy ngokuvamile lwenziwa ngama-cytokines nezidakamizwa ezikhomba izindawo zokuhlola amasosha omzimba.

Amasosha omzimba asebenzisa izindawo zokuhlola ukuze azivikele ekuhlaseleni ajwayelekile noma ama-self-cell emzimbeni. Isebenzisa ama-molecule noma amangqamuzana omzimba omzimba acushiwe noma angasebenzi ukuze aqale impendulo yokuzivikela komzimba. Amangqamuzana omdlavuza angakwazi ukubonwa amasosha omzimba ngoba angaba nama-antigen athile alingisa amangqamuzana omzimba ukuze amasosha omzimba angawahlaseli.

Ama-Cytokines angamakhemikhali amanye amangqamuzana amasosha omzimba angawakha. Alawula ukukhula nokusebenza kwamanye amangqamuzana amasosha omzimba. Kunezinhlobo ezimbili zama-cytokines: ama-interleukin nama-interferon.

Ama-Interleukins asebenza njengophawu lwamakhemikhali phakathi kwamangqamuzana amhlophe egazi. I-Interleukin-2 (IL-2) isiza amangqamuzana amasosha omzimba ukuthi akhule futhi ahlukanise ngokushesha, ngokungeza amaseli e-IL-2 amaningi noma ashukumisayo angakhuphula ukuphendula kwamasosha omzimba kanye nezinga lokuphumelela ngokumelene nomdlavuza othile.

I-Interferon isiza umzimba ukulwa namagciwane, izifo kanye nomdlavuza. Lokhu bakwenza ngokukhulisa amandla amaseli athile omzimba okuhlasela amangqamuzana omdlavuza futhi angase abambezele ukukhula kwamangqamuzana omdlavuza. Ukusetshenziswa kwe-interferon’s kuvunyiwe kuma-cancer afana ne-hair cell leukemia, i-chronic myeologenous leukemia (CML), izinhlobo ze-lymphoma, umdlavuza wezinso, kanye ne-melanoma.

Yini Okusha Ocwaningweni Lwe-Cancer Immunotherapy?

I-Immunotherapy ngokwayo ayiyona insimu entsha, noma isetshenziswa ekwelapheni umdlavuza. Kodwa njengoba kwenziwa ucwaningo olwengeziwe mayelana nokuthi yini ebangela umdlavuza nokuthi singawuthola kanjani kangcono, sikwazi kangcono ukuqhamuka nezindlela zokuzivikela ezifweni futhi silwe.

Izinkampani eziningi ezithaka imithi ziza nemithi yokuqeda umdlavuza. Nakuba kungashiwo okuningi ngemithi ngenkathi kusesigabeni sokuhlela (ngenxa yezizathu zokuphepha), kukhona izivivinyo zomtholampilo ezibonakala zisebenza ngempumelelo ekwelapheni umdlavuza. Omunye umuthi onjalo i-CAR T-cell (Chimeric Antigen Receptor) therapy, i-monoclonal antibody esetshenziselwa ukwelapha i-acute lymphoblastic leukemia.

Lokhu kwelashwa kusebenzisa ama-t-cell aqoqwe egazini lesiguli futhi awenza ngofuzo ukuze akhiqize ama-receptors akhethekile phezulu, ama-chimeric antigen receptors. Isiguli sigonywa ngamaseli amhlophe egazi ashintshiwe, abese efuna futhi abulale amangqamuzana omdlavuza nge-antigen ethile.

UDkt. SA Rosenberg utshele i-Nature Reviews Clinical Oncology ukuthi ukwelashwa kwe-CAR T-cell kungaba “ukwelapha okujwayelekile kwezinye izifo ezibulala ama-B-cell”. ISibhedlela Sezingane sasePhiladelphia senza izivivinyo ze-leukemia ne-lymphoma sisebenzisa i-CAR T-cell therapy. Zonke izimpawu zomdlavuza zanyamalala ezigulini ezingu-27 kwezingu-30, ezingu-19 zalezo ezingu-27 zasala dengwane, abantu abangu-15 abasatholi ukwelashwa, kanti abantu abane basaqhubeka nokuthola ezinye izindlela zokwelapha.

Lokhu kuphawula ukwelashwa okuyimpumelelo kakhulu, futhi ngezinga eliphezulu kangaka lokuyekelela ungabheka phambili ekuboneni ukwelashwa okwengeziwe kwe-CAR T-cell (kanye nokunye okufana nakho) esikhathini esizayo. Ukwelashwa kwe-CAR T-cell “kunamandla kakhulu kunanoma yini esingayithola [njengoba kucatshangelwa ezinye izinhlobo ze-immunotherapy]” kusho uDkt. Crystal Mackall we-National Cancer Institute (NCI).

UDkt. Lee ovela ku-NCI uthi "okutholakele kusikisela ngokuqinile ukuthi i-CAR T-cell therapy iyibhuloho eliwusizo lokufakelwa komnkantsha wethambo ezigulini ezingasabeli ku-chemotherapy". Njengoba izimpawu zokwelashwa kwe-monoclonal antibody zingenzima kakhulu kunokwelapha ngamakhemikhali, kubheka ukuba uhlobo lokwelapha olufaneleka kakhulu nolungacekeli phansi.

Umdlavuza wamaphaphu unezinga eliphansi lokusinda elicishe libe ngu-15% eminyakeni emi-5 uma kuqhathaniswa nomdlavuza webele wama-89%. I-Nivolumab iyisidakamizwa esisetshenziselwa ukwelapha umdlavuza wamaphaphu ongewona omncane kanye ne-melanoma. Ihlolwe eqenjini labangu-129 abanomdlavuza wamaphaphu.

Abahlanganyeli bebenikeza imithamo ye-1, i-3, noma i-10mg/kg yesisindo somzimba we-Nivolumab kuze kufike ezinyangeni ze-96. Ngemuva kweminyaka emi-2 yokwelashwa, izinga lokusinda lalingama-25%, ukwanda okuhle komdlavuza obulalayo njengomdlavuza wamaphaphu. I-Nivolumab iphinde yahlolelwa abantu abane-melanoma, futhi ukuhlolwa kwabonisa ukuthi izinga lokusinda likhuphuke lisuka ku-0% ngaphezu kweminyaka emithathu ngaphandle kokwelashwa kuya ku-40% ngokusetshenziswa kwe-Nivolumab.

Umuthi uvimba i-PD-1 antigen receptor kumaseli amhlophe egazi ukuze amangqamuzana omdlavuza angaxhumani nawo; lokhu kwenza kube lula ukuthi amasosha omzimba abone umdlavuza futhi awulahle ngokufanele. Ngesikhathi sokuhlolwa kwatholakala ukuthi abantu abane-antibody ye-PD-L1 baphendule labo abangenayo, nakuba isizathu salokho singakaziwa.

Kukhona futhi i-DNA immunotherapy, esebenzisa ama-plasmids amangqamuzana omuntu onegciwane ukuze kwakhe umgomo. Uma umgomo ujovwa esigulini ushintsha i-DNA yamaseli athile ukuze kufezwe umsebenzi othile.