Chirwere cheropa
Gomarara rechiropa parizvino ndiro rechishanu rinonyanya kukonzera kufa kuri kuita gomarara pasi rose. Mushonga wemazuva ano wekutanga-systemic treatment inonyanya kunyanya sorafenib, asi kazhinji inongorebesa hupenyu hwose hwemwedzi mitatu, uye ine migumisiro yakakomba.
Muna 2010, immunotherapy yakatanga kubudirira mu melanoma. Kubva ipapo, yakanangana neiyo immunosuppressive molecule PD-1, programmed cell death-ligand 1 (PD-L1), uye cytotoxic T lymphocyte-inobatanidza antigen 4 (CTLA -4) Monoclonal antibodies akabvumidzwa kuti anyore imwe mushure meimwe, kutyora. kuburikidza nenhare yemamota akasiyana akasimba uye kuunza mabhenefiti makuru ekupona kune varwere vane gomarara repamusoro, kusanganisira hepatocellular carcinoma.
Semuyenzaniso, data kubva pachikuva I / II immune checkpoint inhibitors ye advanced hepatocellular carcinoma inoratidza kuti yakagara chinangwa chekupindura mwero wemutsara wekutanga uye wechipiri-mutsara wekushandisa ungangoita 20%. Zvidzidzo zvekiriniki zveanti-PD-1 / anti-PD-L1 zvakasanganiswa nemamwe mamorekuru ekutarisa zviri kuitika zvakare. Pamusoro peimmune checkpoint inhibitors, mamwe maitiro ekushandisa immune system, anosanganisira CAR-T cell NK cell therapy uye peptide vaccine kurwisa hepatocellular carcinoma antigens, akapindawo muzvidzidzo zvePhase I / II. Pazasi isu tichagadzirisa zvakarongeka zvemunhu wese.
Immune checkpoint inhibitor
PD-1 uye PD-L1 / PD-L2
Ma Immune checkpoints ari T maseru epasi mamorekuru ayo anogona kudzvinyirira kana kukurudzira immune system. Zvakakosha, ivo vane basa rekuchengetedza kwavo kushivirira uye kudzivirira zvisina basa kana zvakawandisa mhinduro dzemumuviri.
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 gomarara rechiropa vanopokana neNEXAVAR.
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).
Makiriniki akati wandei emamwe anti-PD-1 / anti-PD-L1 immunotherapy ari kuitika parizvino. (Keynote-240, NCT02702401 uye Keynote-394, NCT03062358) makiriniki maviri echikamu chechitatu achienzanisa keytruda sechipiri chekurapa kwevarwere veHCC vane placebo.
Uye zvakare, akati wandei matsva ekuzvidzivirira immune inhibitors Tislelizumab (anti-PD-1), camrelizumab (anti-PD-1) uye durvalumab (anti-PD-L1) parizvino iri kuongororwa senge yechipiri-mutsetse kurapwa mhinduro mitengo.
CTLA-4
CTLA-4 ndeye CD28 homologue inoratidzwa pane yakagadziriswa T maseru. Inodzvinyirira T cell activation nekukwikwidza iyo ligand B7-1's CD28, iyo inopfuudza chiratidzo chekudzivirira muviri, uyezve ichizopa chiratidzo chinodzivirira kumaT seli.
tremelimumab (tisimumab) ndiyo yega anti-CTLA-4 antibody yakaedzwa se monotherapy kana musanganiswa kurapa mukurapa kwepamusoro HCC. A duku mutyairi kiriniki kuedza 20 viremia varwere vane hepatitis C utachiona (HCV) -yakabatana HCC yakaratidza kuti kwete chete chikamu mhinduro mwero antitumor basa raiva 17.6%, asi yakaratidza antiviral basa uye anokosha utachiona pasi.
Dzimwe nzvimbo dzinoongorora dzinovharira uye ekudzivirira immune
Mukuwedzera kune PD-1 / PD-L1 uye CTLA-4, kune mamwe maitiro ekudzivirira, kusanganisira T cell immunoglobulin mucin 3 (TIM-3) uye lymphocyte activation gene 3 (LAG-3). Miedzo inosanganisa anti-PD-1 / anti-PD-L1 kurapa nemishonga yakanangana neTIM-3 (NCT03099109) uye LAG-3 (NCT03005782 uye NCT01968109) atoenderera mberi.
Yakasanganiswa immunotherapy zano rekenza yechiropa yakakwira
Kunyangwe iyo yekupindura mwero weiyo imwechete-mumiririri kurapwa ne immune checkpoint inhibitors yakanyanyisa kupfuura chiyero chekupindura chesorafenib, asi zvakazara ichiri yakaderera kwazvo (<20%). Naizvozvo, mukiriniki, isu tinoramba tichiongorora nzira dzekuwedzera mhinduro yemurwere. Semuenzaniso, kusanganiswa kwema immune checkpoint inhibitors nemamwe ma checkpoint inhibitors, madiki mamorekuru kinase inhibitors, mamwe maratidziro ehurongwa uye emuno.
Chikamu cheI / II kuyedzwa kwekubatanidzwa kwe devarumab (durvalumab) uye temlimumab (tremelimumab) yekenza yechiropa yakakwira yakaratidza mwero wekupindura we20% pasina zviitiko zvakakomba zvakashata. Chikamu chechitatu III kudzidza (NCT03298451) chemubatanidzwa wekurapa-mutsara wekutanga kurapwa parizvino kuri kutorwa.
Kuwirirana pakati pe immune checkpoint inhibitors nemishonga yemuno (kusanganisira ablation, radiation therapy uye transarterial chemoembolization (TACE)) iri kuferefetwa. Mabundu ane yakaderera mutation mutoro uye mashoma maantigens matsva anowanzo mashoma immunogenic uye haana / yakaderera mhinduro (kana yekutanga kuramba) kune chekipoint inhibitors. Kurapwa kwenzvimbo uye kurapwa nemwaranzi kunokonzeresa kuzvimba uye kuburitsa maantigen matsva anoburitswa muropa. Naizvozvo, musanganiswa wecheki inhibitors uye yemuno nharaunda therapy inotarisirwa kuwedzera kunzwa kune checkpoint inhibitors.
Muchidzidzo chekutanga chevarwere makumi matatu nevaviri, temlimumab (tremelimumab) yakashandiswa pamwe chete neradiofrequency ablation kana TACE. Kuita kwakasarudzika kunoonekwa mune inosvika 32% yevarwere.
Dhipatimendi rezvehutano reGlobal Oncologist Network rinoronga izvozvi zvekiriniki miedzo yeunonotherapy cheki yekudzivirira inhibitor monotherapy uye yekubatanidza kurapa mune inotevera tafura yekutarisa kwako. Avo vanoda kutora chikamu vanogona kufonera dhipatimendi rekurapa kuti vatange vaongorora.
Immune cell kurapa
MOTA-TOTSI CHIRAPO
T cells engineered with chimeric antigen receptors (CAR) gain the ability to recognize certain antigens, which allows specific cells (including tumarara 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.
NK sero kurapa
NK (chaiyo mhondi cell, NK) ndiyo immune cell ine yakasimba kwazvo anti-cancer maitiro. Nzvimbo ine simba kwazvo ndeyekuti inogona zvakananga uye nekukurumidza mutorwa mutorwa mitezo yekune dzimwe nyika (hutachiona uye hutachiona hutachiona) pasina maitiro ehurukuro yeantigen uye pasina vamwe vanhu vanotaura. Masero, maseru ekenza, maseru enescent, nezvimwewo)
NK maseru, se "Molecular Patrol", inofamba muropa. Kana vachinge vawana maseru ekunze kana masero akachinja ekuzvizivisa (anonzi MHC), iyo NK cell's receptor pakarepo inotumira chiratidzo uye inomhanyira kune yakanangana nesero membrane. Ndokureva kuti, maseru eNK anofanirwa kunge ari kumberi kwehondo. Inoburitsa maturu ane chepfu kwairi, nekukurumidza inoparadza maseru akanangwa, uye inoita kuti maseru ekenza afe mukati memaminitsi mashanu.
Izvo zvinofanirwa kucherechedzwa kuti NK maseru, sechikamu chepakati chemuviri wemuviri, ndiwo akakosha maseru emukati emuviri mumuviri wemunhu, asi iwo asingawanzo kuwanikwa muropa revanhu, iro rinoverengera chete 5% -10% yema lymphocyte. Masero anoverengera 30-50% yema lymphocyte muropa rechiropa chemunhu. Inofananidzwa nekutenderera NK masero, NK maseru muchiropa ane yakasarudzika phenotypic hunhu uye hunhu hunhu, kuratidza yakakwira cytotoxicity kune tumarara maseru. Munguva yekuitika kwekenza yechiropa, huwandu hwenhengo dzeNK uye mashandiro ecytokine (interferon-γ) kugadzirwa uye cytotoxic chiitiko chakaderedzwa. Naizvozvo, marapirwo anomutsiridza NK maseru uye oashandisa kurwisa mamota incl
ude chemoimmunotherapy uye kutora kwekutora kweNK masero. Ikozvino pane 7 chikamu I / II kiriniki miedzo ichiongorora NK cell-based immunotherapy muHCC varwere, mazhinji acho anotora kutora kwekutora kwema autologous kana allogeneic NK maseru.
Mushonga wePeptide
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.
Chikamu chekutanga ini chidzidzo chevarwere makumi matatu nevatatu vane HCC yepamusoro vachishandisa GPC33 peptide jekiseni yakaratidza kuti jekiseni raive rakabvumirwa, murwere 3 aive nekanganwirwo (1%), uye varwere gumi nevatanhatu vaive nehutano hwakasimba pamwedzi miviri (3%) Makumi mapfumbamwe muzana evarwere vakagadzira cytotoxic T lymphocyte mhinduro mushure mekunyorwa pamwe neiyo chaiyo GPC19 jekiseni, iyo yaibatanidzwa nekupona kwese. Iko kusanganisa kushandiswa kweiyo GPC2 peptide jekiseni uye kumwe kurapa parizvino kuri kuongororwa.
Mashoko evarwere vegomarara rechiropa
Takapinda munguva itsva mukurapa kwehepatocellular carcinoma, umo mazano anobva pane immune checkpoint inhibitors achakurumidza kuva nheyo, kana se monotherapy kana pamwe chete nemamwe checkpoint inhibitors uye kinase inhibitors. Uye zvakare, mutsva weImmunotherapy tsvakiridzo uye budiriro yakaunzawo tariro yakawanda uye nzira dzekurapa kune varwere vepamberi. Nekuti kune miedzo yekiriniki yakawandisa, hazvigoneke kuisuma imwe neimwe muchinyorwa chino.
