Kansarka beerka
Kansarka beerka ayaa hadda ah sababta shanaad ee ugu badan ee dhimashada kansarka la xiriirta ee adduunka. Daawada daawaynta habaysan ee safka hore ee hadda jirta waxa ay u badan tahay sorafenib, laakiin badiyaa waxa ay dheeraysaa oo kaliya badbaadada guud ee 3 bilood, waxaanay leedahay waxyeelooyin halis ah.
Sannadkii 2010, daawaynta difaaca jirka ayaa markii ugu horreysay ku guulaysatay melanoma. Tan iyo markaas, waxay bartilmaameedsatay unugyada difaaca jirka ee PD-1, barnaamijka dhimashada unugyada unugyada 1 (PD-L1), iyo cytotoxic T lymphocyte antigen 4 (CTLA-4) unugyada difaaca jirka ee Monoclonal ayaa loo oggolaaday inay midba midka kale taxaan, jabiso. iyada oo loo marayo qalcadda burooyin adag oo kala duwan oo keenaya faa'iidooyin badbaado oo weyn bukaannada qaba kansarka horumarsan, oo ay ku jiraan kansarka hepatocellular.
Tusaale ahaan, xogta laga helay marxaladda I/II ee isbaarada difaaca ee ka hortagga kansarka hepatocellular sare waxay muujinaysaa in heerka jawaabta ujeeddada waara ee isticmaalka safka koowaad iyo labaad uu yahay ilaa 20%. Daraasadaha kiliinikada ee anti-PD-1 / anti-PD-L1 oo ay weheliso unugyo kale oo isbaaro ayaa sidoo kale socda. Ka sokow isbaarooyinka difaaca jirka, xeeladaha kale ee loo isticmaalo habka difaaca jirka, oo ay ku jiraan CAR-T cell therapy cell iyo tallaalada peptide ee ka hortagga kansarka hepatocellular carcinoma antigens, ayaa sidoo kale galay daraasadaha Wajiga I / II. Hoos waxaan si nidaamsan u qiimeyn doonaa qof walba.
Kahortaga isbaarada isdifaaca
PD-1 iyo PD-L1 / PD-L2
Isbaarada difaacu waa unugyo dusha sare ee unug T ah oo xakameyn kara ama kicin kara habka difaaca jirka. Muhiimad ahaan, waxay mas'uul ka yihiin ilaalinta dulqaadkooda iyo ka hortagga jawaabaha difaaca ee aan loo baahnayn ama xad-dhaaf ah.
On September 22, 2017, based on a 214-person Phase 2 clinical trial Checkmate-040, the US FDA approved the PD-1 antibody Opdivo for patients with advanced kansarka beerka kuwaas oo u adkaysta NEXAVAR.
On November 9, 2018, the US FDA approved the immunotherapy drug pembrolizumab (Pembrolizumab, Keytruda) to treat patients with advanced liver cancer (hepatocellular carcinoma). It is suitable for patients with hepatocellular carcinoma who have previously been treated with too much Gemira (Sorafenib).
Dhowr tijaabo oo caafimaad oo kale oo ka hortagga PD-1 / anti-PD-L1 immunotherapy ayaa hadda socda. (Kaynote-240, NCT02702401 iyo Keynote-394, NCT03062358) waa laba waji oo tijaabo caafimaad ah oo isbarbar dhigaya keytruda oo ah daawaynta safka labaad ee bukaanada HCC ee horumarsan ee leh placebo.
Intaa waxaa dheer, dhowr xakameyn cusub oo difaaca difaaca Tislelizumab (anti-PD-1), camrelizumab (anti-PD-1) iyo durvalumab (anti-PD-L1) ayaa hadda lagu qiimeeyaa heerarka jawaabta daaweynta ee labaad.
CTLA-4
CTLA-4 waa CD28 homologue oo lagu muujiyay unugyada T ee firfircoon. Waxay xakameysaa firfircoonida unugyada T-ga iyadoo u tartamaysa ligand B7-1's CD28, kaas oo gudbiya calaamadda difaaca jirka, oo iyaduna keenta calaamad ka hortag ah unugyada T.
tremelimumab (tisimumab) waa ka-hortagga-CTLA-4-ka-hortagga kaliya ee lagu tijaabiyay monotherapy ama isku darka daaweynta HCC sare. Tijaabo tijaabo ah oo yar oo tijaabo ah oo lagu sameeyay 20 bukaan oo viremia qaba fayraska cagaarshow C (HCV) ee la xidhiidha HCC ayaa muujisay in aanay ahayn oo kaliya heerka jawaabta qayb ahaan ee waxqabadka antitumor ay ahayd 17.6%, laakiin sidoo kale waxay muujisay firfircoonida fayraska iyo culayska fayraska ee Down.
Isbaarooyinka kale ee ka hortagga iyo isbaarooyinka difaaca
Marka lagu daro PD-1 / PD-L1 iyo CTLA-4, waxaa jira soo-dhoweeyayaal kale oo xannibaya, oo ay ku jiraan T-cell immunoglobulin mucin 3 (TIM-3) iyo hidda-wadaha firfircoonida lymphocyte 3 (LAG-3). Tijaabooyin isku daraya daawaynta ka hortagga PD-1 / ka-hortagga PD-L1 iyo dawooyinka lagu beegsanayo TIM-3 (NCT03099109) iyo LAG-3 (NCT03005782 iyo NCT01968109) ayaa mar hore socday.
Istaraatiijiyad isku-darka difaaca jirka ee kansarka beerka ee horumarsan
Inkasta oo heerka jawaabta ee daaweynta hal wakiil ah ee xakameynaya isbaarada difaaca ay aad uga badan tahay heerka jawaabta sorafenib, laakiin guud ahaan wali waa mid aad u hooseeya (<20%). Sidaa darteed, gudaha rugta caafimaadka, waxaan sii wadeynaa sahaminta xeeladaha lagu kordhinayo jawaabta bukaanka. Tusaale ahaan, isku-darka isbaarada difaaca iyo isbaarada kale ee isbaarada, molecule kinase inhibitors yar, daawaynta kale ee habdhiska iyo deegaanka.
Marxaladda I / II ee isku darka devarumab (durvalumab) iyo temlimumab (tremelimumab) ee kansarka beerka ee sare u kacay waxay muujisay heerka jawaabta 20% iyada oo aan la helin dhacdooyin xun oo halis ah. Daraasad wejiga III ah (NCT03298451) ee isku darka daaweynta safka koowaad ayaa hadda la qorayaa.
Is-dhexgalka ka dhexeeya horjoogayaasha isbaarada difaaca iyo daawaynta maxalliga ah (ay ku jiraan ka-baxa, daawaynta shucaaca iyo chemoembolization transarterial (TACE)) ayaa sidoo kale la baarayaa. Burooyinka leh culeyska isbeddelka hooseeya iyo antigen-yada cusub oo yar ayaa guud ahaan ka yar difaaca jirka mana laha jawaab celin hoose (ama iska caabin aasaasiga ah) ee horjoogayaasha isbaarada. Daaweynta maxalliga ah iyo daaweynta shucaaca ayaa keena caabuq waxayna soo saaraan antigens cusub oo lagu sii daayo dhiigga. Sidaa darteed, isku darka isbaarooyinka isbaarada iyo daawaynta deegaanka ayaa la filayaa inay kordhiso dareenka horjoogayaasha isbaarada.
Daraasad horudhac ah oo lagu sameeyay 32 bukaan, temlimumab (tremelimumab) ayaa loo adeegsaday iyadoo lagu daray soo-baxa shucaaca ama TACE. Falcelinta qayb ahaan ayaa lagu arkay ilaa 25% bukaanada.
Waaxda caafimaadka Shabakadda Oncologist Global waxay taxdaa tijaabooyinka caafimaad ee imminka ee isbaarada isbaarada difaaca ee monotherapy iyo daawaynta isku dhafka ah shaxdan soo socota ee tixraacaaga. Kuwa raba inay ka qaybqaataan waxay wici karaan waaxda caafimaadka qiimayn horudhac ah.
Daaweynta unugyada difaaca jirka
CAR-T CELL therapy
T cells engineered with chimeric antigen receptors (CAR) gain the ability to recognize certain antigens, which allows specific cells (including buro cells) to be targeted. CAR-T-based therapy has successfully treated CD19-positive hematological malignancies, which paved the way for its application in solid tumors. In HCC, Glypican-3 (GPC3) is most commonly used as a target for CAR-T therapy and has significant antitumor activity both in vitro and in vivo. Second, alpha-fetoprotein (AFP), which is usually overexpressed in HCC, is also used as a target and has a potent anti-tumor response. There are currently at least 10 phase I / II clinical trials (almost all conducted in China) to study the application of CAR-T cells in advanced HCC.
Daaweynta unugyada NK
NK (unugga dilaaga dabiiciga ah, NK) waa unugga difaaca ee leh saamaynta ugu xooggan ee ka hortagga kansarka. Meesha ugu awoodda badan waa in ay si toos ah oo degdeg ah u soo saari karto shisheeye shisheeye ah (infekshannada fayraska iyo bakteeriyada) iyada oo aan la marin habka antigen-ka iyo iyada oo aan dadka kale soo sheegin. Unugyada, unugyada kansarka, unugyada dareenka, iwm.)
Unugyada NK, sida "Molecular Patrol", waxay roondeeyaan socodka dhiigga. Marka ay helaan unugyo qalaad ama unugyo mutant ah oo lumiyey is-aqoonsigoodii (oo loo yaqaan MHC), soo-dhoweeyaha unugga NK wuxuu isla markiiba soo diraa calaamad wuxuuna u yaacay xuubka unugyada bartilmaameedka ah. Taasi waa in la yiraahdo, unugyada NK waa inay ku jiraan safka hore ee dagaalka. Waxa ay ku sii daysaa walxaha sunta ah, waxa ay si degdeg ah u milmaysaa unugyada la beegsanayo, waxaanay sababtaa in unugyada kansarka ay ku dhintaan 5 daqiiqo gudahood.
Waa in la ogaadaa in unugyada NK, oo ah qaybta udub-dhexaadka ah ee habka difaaca jirka, ay yihiin kuwa ugu qiimaha badan unugyada difaaca jirka ee jidhka bini'aadamka, laakiin aad bay ugu yar yihiin dhiigga xuubka bini'aadamka, oo xisaabiya kaliya 5% -10% lymphocytes. Unugyadu waxay ku xisaabtamaan 30-50% lymphocytes ee beerka beerka aadanaha. Marka la barbardhigo unugyada NK ee wareegaya, unugyada NK ee beerka waxay leeyihiin sifooyin phenotypic gaar ah iyo sifooyin shaqeynaya, oo muujinaya cytotoxicity sare unugyada burooyinka. Inta lagu jiro dhacdooyinka kansarka beerka, saamiga unugyada NK iyo shaqada cytokine (interferon-γ) wax soo saarka iyo dhaqdhaqaaqa cytotoxic waa la dhimay. Sidaa darteed, daawaynta dib u hawlgeliya unugyada NK oo u isticmaala inay weeraraan burooyinka oo ay ku jiraan
ude chemoimmunotherapy iyo tallaalka korsashada ee unugyada NK. Hadda waxaa jira 7 waji I / II tijaabooyin caafimaad oo baaraya unugyada difaaca jirka ee NK ee bukaannada HCC, kuwaas oo intooda badan wareejinta korsashada ee unugyada autologous ama allogeneic NK.
Tallaalka Peptide
Cancer peptide vaccine is the same as CAR-T cell immunotherapy. The most studied peptide vaccine for hepatocellular carcinoma is GPC3, because it is overexpressed in up to 80% of liver cancers (including early tumors), but not in normal tissues. It is very specific Target. In addition, its expression is associated with a poor prognosis.
Marxaladda horudhaca ah ee I ee daraasadda 33 bukaan oo qaba HCC horumarsan oo isticmaalaya tallaalka GPC3 peptide waxay muujisay in tallaalka si wanaagsan loo dulqaatay, 1 bukaan ayaa qayb ahaan cafiyay (3%), iyo 19 bukaan ayaa qabay cudur deggan 2 bilood (58%). Boqolkiiba 3 bukaannada ayaa sameeyay jawaab celin cytotoxic T lymfosayt ka dib markii la geliyay tallaal gaar ah oo GPC3 ah, kaas oo la xiriiray badbaadada guud. Isticmaalka isku-darka ah ee tallaalka peptide GPCXNUMX iyo daawaynta kale ayaa hadda si dheeraad ah loo sahamiyay.
Erayada loogu talagalay bukaanka kansarka beerka
Waxaan galnay xilli cusub oo ku saabsan daaweynta kansarka hepatocellular, kaas oo xeeladaha ku salaysan isbaarada difaaca difaacu ay dhowaan noqon doonaan aasaaska, ha ahaato monotherapy ama marka lagu daro xannibayaasha kale ee isbaarada iyo kinase inhibitors. Intaa waxaa dheer, cilmi-baarista cusub ee Immunotherapy iyo horumarinta ayaa sidoo kale keenay rajooyin iyo fursado daaweyn oo dheeraad ah bukaannada sare. Sababtoo ah waxaa jira tijaabooyin caafimaad oo aad u badan, suurtagal maaha in mid mid loo soo bandhigo maqaalkan.
