Mefuta ea Immunotherapy bakeng sa Kalafo ea Kankere
Kalafo ea 'mele ke mokhoa oa kalafo ea kankere o sebelisang sesole sa 'mele ho lemoha le ho loantša lisele tsa kankere. Ho fapana le chemotherapy, e hlaselang lisele tse arohanang ka potlako, kapa radiotherapy, e senyang DNA ea sele ea hlahala ka mahlaseli, immunotherapy e sebetsa ka ho "eketsa," "ho tataisa," kapa "ho lokolla li-brake" karabelong ea 'mele ea ho itšireletsa mafung, e leng se etsang hore 'mele o atlehe haholoanyane ho timetsa kankere. Lilemong tsa morao tjena, immunotherapy e fetohile tsoelo-pele e kholo ho oncology hobane e ka fana ka likarabo tse tšoarellang ho bakuli ba bang, esita le ho kankere eo pele e neng e le thata ho e phekola.
Leha ho le jwalo, kalafo ya immunotherapy ha e a lokela mefuta yohle ya kankere kapa bakudi bohle. Ditlamorao di ka fapana le mekhoa ya phekolo e tlwaelehileng, hangata e amanang le ho sebetsa ho feteletseng ha sesole sa mmele. Ka hona, kgetho ya kalafo ya immunotherapy hangata e itshetlehile ka mofuta wa kankere, mohato wa lefu, boemo ba mokuli, le di-biomarker tse itseng. Tse latelang ke mefuta e tlwaelehileng haholo ya kalafo ya immunotherapy e sebediswang kalafong ya kankere.
1. Lithibela-mafu tsa ho Thibela-mafu (Lithibela-mafu tsa ho Thibela-mafu)
E 'ngoe ea mefuta e tsebahalang haholo ea phekolo ea 'mele ea ho itšireletsa mafung ke lithibela-mafu tsa ho hlahloba' mele. Tsamaiso ea 'mele ea ho itšireletsa mafung e na le "libaka tsa ho hlahloba," mekhoa ea tlhaho e thibelang likarabelo tse feteletseng tsa 'mele tsa ho itšireletsa mafung tse ka senyang lisele tsa' mele. Hangata lisele tsa kankere li sebelisa libaka tsena tsa ho hlahloba ho "ipata" tlhaselong ea lisele tsa T (lisele tsa 'mele tsa ho itšireletsa mafung tse bolaeang).
Lithibela-mafu tsa Checkpoint li sebetsa ka ho thibela liprotheine tse itseng tsa Checkpoint, li lumella lisele tsa T ho tsosolosa le ho hlasela lisele tsa mofetše. Lipheo tse peli tse tloaelehileng haholo ke:
– PD-1/PD-L1 (Lefu le Entsoeng ka Lenaneo-1 / Ligand-1): Lisele tsa mofetše li ka hlahisa PD-L1 ho "tima" lisele tsa T. Meriana e thibelang PD-1 kapa PD-L1 e ka thusa ho bula tšebetso ea lisele tsa T hape.
– CTLA-4 (Cytotoxic T-Lymphocyte–Associated Protein 4): CTLA-4 ke thibelo ya ho kenngwa tshebetsong ha sele ya T, haholoholo mehatong ya pele ya karabelo ya mmele ya ho itšireletsa mafung.
Lithibela-mafu tsa Checkpoint li sebelisetsoa ho phekola mefuta e fapaneng ea kankere, ho kenyeletsoa melanoma, kankere ea matšoafo, kankere ea liphio, kankere ea senya, le mefuta e meng ea kankere ea hlooho le molala. Molemo oa phekolo ena ke monyetla oa karabelo e tšoarellang nako e telele, empa likotsi li kenyelletsa litla-morao tsa autoimmune tse kang colitis, pneumonitis, mathata a thyroid, esita le lefu la sebete la autoimmune.
2. Kalafo ea Lisele tsa CAR T (Kalafo ea Lisele tsa CAR T)
Kalafo ea lisele tsa CAR T ke kalafo ea 'mele e etselitsoeng motho ka mong haholo. Kalafong ena, lisele tsa T tsa mokuli li nkuoa maling ebe li fetoloa laboratoring hore li be le receptor e khethehileng e bitsoang Chimeric Antigen Receptor (CAR). Mokelikeli ona o etselitsoe ho lemoha li-antigen tse itseng holim'a lisele tsa kankere. Hang ha li fetotsoe le ho ata, lisele tsa T li khutlisetsoa 'meleng oa mokuli ho ea batla le ho senya lisele tsa kankere ka sepheo se seholo.
Kalafo ea lisele tsa CAR T e bontšitse katleho e kholo haholo-holo mefuteng e itseng ea kankere ea mali, joalo ka:
– acute lymphoblastic leukemia (ALL) maemong a mang,
- li-lymphoma tse ling tse seng tsa Hodgkin,
– myeloma e mengata ka matšoao a itseng.
Leha ho le jwalo, kalafo ena e ka boela ya baka ditlamorao tse mpe, tse kang Cytokine Release Syndrome (CRS), e bakang feberu e phahameng le kgatello e tlase ya madi, hammoho le mathata a itseng a methapo ya kutlo. Ho feta moo, ditjeo le ho fumaneha ha setsi ke diphephetso ka lebaka la tshebetso e rarahaneng.
3. Li-antibodies tsa monoclonal
Li-antibodies tsa monoclonal ke liprotheine tsa maiketsetso tse etselitsoeng ho hokela lipheo tse itseng liseleng tsa kankere. Ka ho "tšoaea" lisele tsa kankere, li-antibodies li thusa sesole sa 'mele ho lemoha lihlahala kapa ho sitisa matšoao a kholo ea kankere.
Ho na le litsela tse 'maloa tseo li-antibodies tsa monoclonal li sebetsang ka tsona kankere:
1. Li-antibodies tse shebaneng le li-receptor: li thibela matšoao a kholo liseleng tsa mofetše.
2. Li-antibodies tse bakang timetso ke sesole sa 'mele: li hohela lisele tsa 'mele ho hlasela lisele tse tšoailoeng.
3. Conjugate ea antibody-drug (ADC): li-antibodies li jara "moroalo o moholo" oa meriana ea chemotherapy ho ea liseleng tsa kankere e le hore li shebane haholoanyane.
4. Kalafo ea radioimmunotherapy: li-antibodies li isa lintho tse ntšang mahlaseli a kotsi ho hlahala.
Li-antibodies tsa monoclonal li sebelisoa haholo ho phekola mefuta e fapaneng ea mofetše, ho kenyeletsoa mofetše oa matsoele , lymphoma, mofetše oa mala a maholo, le tse ling. Litla-morao lia fapana, ho tloha liketsong tsa ho kenngoa ha mali le makhopho a letlalo ho isa tšenyo ea litho, ho latela sepheo seo li se shebileng.
4. Liente tsa Kankere
Liente tsa kankere li reretsoe ho susumetsa sesole sa 'mele ho lemoha li-antigen tsa kankere. Ho fapana le liente tsa ho thibela mafu a tšoaetsanoang , liente tsa kankere li arotsoe ka mekhahlelo e 'meli e meholo:
– Meento e thibelang: thibela kankere e bakoang ke likokoana-hloko tse itseng. Mohlala o tsebahalang haholo ke ente ea HPV, e fokotsang kotsi kankere ea molomo oa popelo le kankere tse ling tsa hlooho le molala, hammoho le ente ea hepatitis B ho fokotsa kotsi ea kankere ea sebete.
– Meento ea phekolo: e fuoa bakuli ba seng ba ntse ba e-na le kankere ho thusa sesole sa 'mele ho hlasela hlahala.
Hangata liente tsa phekolo li shebana le li-antigen tse ikhethileng ho hlahala ea mokuli kapa li-antigen tse tloaelehileng ho mefuta e itseng ea kankere. Likarabelo li ka fapana, 'me lipatlisiso li ntse li tsoela pele ho ntlafatsa katleho, ho kenyeletsoa le ho sebelisa metsoako ea lithibela-mafu tsa checkpoint.
5. Kalafo ea Cytokine
Li-cytokine ke lipontšo tsa limolek'hule tseo lisele tsa 'mele li li sebelisang ho buisana le ho laola likarabelo tsa 'mele. Kalafong ea kankere, li-cytokine tse itseng li ka fanoa ho ntlafatsa ts'ebetso ea sistimi ea 'mele ea ho itšireletsa mafung.
Mehlala ea li-cytokine tse 'nileng tsa sebelisoa haholo li kenyelletsa:
– Interleukin-2 (IL-2): e ka susumetsa ho ata ha lisele tsa T le lisele tsa NK (natural killer). E sebelisitsoe ho kankere e itseng ea liphio le melanoma.
– Interferon alpha: e ka ntlafatsa karabelo ea 'mele ea ho itšireletsa mafung' me e na le litlamorao tse thibelang ho ata ha mafu ho mefuta e meng ea kankere.
Kalafo ea cytokine e ka sebetsa ho bakuli ba bang, empa hangata e na le litla-morao tse mpe tse kang feberu, mokhathala o matla, khatello e tlase ea mali, le ts'ebetso e mpe ea litho, kahoo ts'ebeliso ea eona joale e khetha haholoanyane 'me hangata e nkeloa sebaka ke mekhoa ea phekolo e khethehileng ea' mele ea ho itšireletsa mafung.
6. Kalafo ea vaerase ea Oncolytic
Kalafo ea kokoana-hloko ea oncolytic e sebelisa livaerase tse fetotsoeng ho tšoaetsa le ho senya lisele tsa kankere, ha ka nako e ts'oanang e "tsosa" sesole sa 'mele ho lemoha hlahala. Ha kokoana-hloko e senya (e senya) lisele tsa kankere, li-antigen tsa hlahala lia lokolloa, e leng se bakang karabelo e pharaletseng ea 'mele ea ho itšireletsa mafung.
Kalafo ena e ipiletsa hobane e sebetsa ka mekhoa e 'meli: ho timetsoa ha lisele tsa hlahala ka kotloloho le ho kenya tšebetsong sesole sa 'mele se loantšang kankere. Hangata e fanoa ka ente e tobileng ka har'a hlahala. Lipatlisiso li ntse li tsoela pele ho atolosa tšebeliso ea eona ho pholletsa le mefuta e fapaneng ea kankere le ho e kopanya le lithibela-mafu tsa checkpoint bakeng sa karabelo e matla haholoanyane.
7. Kalafo ea TIL le Kalafo e 'Ngoe ea Immunotherapy ea Lisele tse Amoheloang
Ntle le CAR T, ho na le mekhoa e meng e bitsoang kalafo ea sele e amoheloang, joalo ka phekolo ea li-lymphocyte tse kenang ka har'a tumor (TIL). Kalafong ea TIL, lingaka li nka lisele tsa 'mele tse seng li ntse li le teng liseleng tsa hlahala (li-lymphocyte tse "kenang" ka har'a hlahala), li li atise ka laboratoring, ebe li li khutlisetsa ho mokuli. Hobane lisele tsena li "koetliselitsoe" ho lemoha tikoloho ea hlahala, phekolo ena e ka sebetsa maemong a mang, haholo-holo maemong a lipatlisiso le litsi tse itseng tsa mofetše.
Hape ho na le mekhoa ea ho etsa lisele tsa T ka li-receptor tse ling (mohlala, lisele tsa T tse entsoeng ka TCR), tse shebaneng le li-antigen tsa hlahala ka mokhoa o fapaneng oa ho lemoha ho feta li-CAR.
Kalafo ea 'Mele ea ho Imolla Motsoako le Liphephetso tsa Nakong e Tlang
Tshebetsong ea bongaka , phekolo ea 'mele ea ho itšireletsa mafung hangata e kopanngoa le chemotherapy, radiotherapy, phekolo e reretsoeng, kapa motsoako oa li-immunotherapy. Sepheo ke ho eketsa monyetla oa karabelo, ho hlōla khanyetso, le ho atolosa palo ea bakuli ba ka ruang molemo.
Leha ho le jwalo, ho ntse ho na le diphephetso tsa bohlokwa, tse kang:
– ha se bakuli bohle ba arabelang,
– ho bolela esale pele karabelo ho hloka di-biomarker tse nepahetseng (mohlala, tlhahiso ya PD-L1, moroalo wa diphetoho tsa hlahala, MSI-e phahameng dikankereng tse itseng),
- litla-morao tsa autoimmune li lokela ho beoa leihlo ka hloko,
– phihlello le litšenyehelo tsa kalafo e ntse e le bothata libakeng tse ngata.
Ho koala
Kalafo ea 'mele e fetotse sebaka sa kalafo ea mofetše ka ho fana ka mokhoa o mocha oa ho sebelisa matla a sesole sa 'mele . Mekhoa ena e fapana ho tloha ho li-checkpoint inhibitors, kalafo ea lisele tsa CAR T, li-antibodies tsa monoclonal, liente tsa mofetše, phekolo ea cytokine, livaerase tsa oncolytic, le mekhoa ea kalafo ea lisele tse amohelang tse kang TILs. Mokhoa o mong le o mong o na le melemo e ikhethang, meeli le matšoao. Ka hona, liqeto mabapi le kalafo ea 'mele li lokela ho etsoa ka ho buisana le ngaka ea mofetše, ho nahanoa ka mofuta oa mofetše, boemo ba mokuli, le li-biomarker tse amehang. Ka lipatlisiso tse tsoelang pele, phekolo ea 'mele e lebelletsoe ho ba e sebetsang haholoanyane, e sireletsehileng haholoanyane, le e fumanehang habonolo ho bakuli ba mofetše.
