Ciwon daji
Cutar sankarar hanta a halin yanzu ita ce ta biyar mafi yawan sanadin mutuwar da ke da alaƙa da cutar daji a duniya. Maganin jiyya na tsarin layi na farko na yanzu shine sorafenib, amma yawanci yana tsawaita rayuwar tsawon watanni 3 kawai, kuma yana da mummunar illa.
A cikin 2010, immunotherapy ya fara nasara a cikin melanoma. Tun daga wannan lokacin, an yi niyya ga kwayoyin immunosuppressive PD-1, shirye-shiryen mutuwa-ligand 1 (PD-L1), da kuma cytotoxic T lymphocyte-abokan antigen 4 (CTLA-4) Monoclonal antibodies an yarda da su don jera daya bayan daya, karya. ta kagara na daban-daban m ciwace-ciwacen daji da kuma kawo babbar rayuwa fa'ida ga marasa lafiya da ci-gaba ciwon daji, ciki har da hepatocellular carcinoma.
Misali, bayanai daga mataki na I/II masu hana wuraren bincike na rigakafi na ci-gaba na ciwon hanta sun nuna cewa ƙimar amsawar haƙiƙa mai ɗorewa don amfani da layin farko da na biyu kusan kashi 20%. Nazarin asibiti na anti-PD-1/anti-PD-L1 a haɗe tare da wasu ƙwayoyin ma'aunin bincike suma suna kan gudana. Bugu da ƙari ga masu hana wuraren bincike na rigakafi, wasu dabarun amfani da tsarin rigakafi, gami da CAR-T cell NK cell therapy da peptide alluran rigakafin cutar sankara na hepatocellular carcinoma antigens, suma sun shiga karatun Phase I / II. A ƙasa za mu dauki tsari ga kowa da kowa.
Mai hana shigowar shinge
PD-1 da PD-L1 / PD-L2
Abubuwan dubawa na yau da kullun sune ƙwayoyin T cell wanda zasu iya dakatar ko haɓaka tsarin rigakafi. Mahimmanci, suna da alhakin kiyaye haƙurin kansu da hana amsoshin rigakafi marasa mahimmanci ko wuce gona da iri.
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 ciwon daji wanda ke jure wa 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).
Yawancin gwaji na asibiti na wasu anti-PD-1 / anti-PD-L1 immunotherapy suna gudana a halin yanzu. (Maɓalli-240, NCT02702401 da Keynote-394, NCT03062358) gwaje-gwajen gwaji ne na kashi na III na gwaji waɗanda ke kwatanta keytruda a matsayin jiyya na layi na biyu don ci gaban HCC marasa lafiya tare da placebo.
Bugu da kari, da yawa sabbin masu hana ruwa kariya masu kariya Tislelizumab (anti-PD-1), camrelizumab (anti-PD-1) da durvalumab (anti-PD-L1) a halin yanzu ana kimanta su azaman matakan martanin jiyya na biyu.
Saukewa: CTLA-4
CTLA-4 haɗin haɗin CD28 ne wanda aka bayyana akan ƙwayoyin T masu aiki. Yana danne kunnawar T ta hanyar yin gasa don B7-1's CD28, wanda ke watsa sigina na rigakafi, sannan kuma yana bayar da siginar hanawa zuwa kwayoyin T.
tremelimumab (tisimumab) shine kawai maganin anti-CTLA-4 da aka gwada azaman monotherapy ko haɗin haɗin gwiwa a cikin jiyya na ci gaba na HCC. Wani ƙaramin gwaji na gwaji na gwaji na 20 masu cutar viremia masu cutar hanta (HCV) mai alaƙa da HCC ya nuna cewa ba kawai ƙimar amsawar aikin antitumor ba shine 17.6%, amma kuma ya nuna aikin antiviral da babban nauyin hoto mai hoto Down.
Sauran wuraren bincike da hana kariya
Baya ga PD-1 / PD-L1 da CTLA-4, akwai wasu masu karɓa na hanawa, ciki har da T cell immunoglobulin mucin 3 (TIM-3) da kwayar halittar kwayar lymphocyte 3 (LAG-3). Gwaje-gwajen da ke tattare da maganin-PD-1 / anti-PD-L1 tare da kwayoyi masu niyya ga TIM-3 (NCT03099109) da LAG-3 (NCT03005782 da NCT01968109) sun riga sun fara.
Haɗin dabarun rigakafin rigakafin rigakafin ciwon hanta mai ci gaba
Kodayake yawan amsar magani na wakili guda tare da masu hana kariya na kariya ya wuce matakin martani na sorafenib, amma gaba daya har yanzu yana da rauni sosai (<20%). Sabili da haka, a cikin asibitin, muna ci gaba da bincika dabarun don ƙara ƙarfin haƙuri. Misali, haduwa da masu hana masu kariya na kariya tare da wasu masu hana ruwa gudu, kananan masu hana kwayar halitta, sauran hanyoyin magani da na gida.
Gwajin I / II na zamani na haɗuwa da devarumab (durvalumab) da temlimumab (tremelimumab) don ci gaba da cutar kansa hanta ya nuna adadin amsa na 20% ba tare da wani mummunan abu ba. Nazarin lokaci na III (NCT03298451) na wannan haɗin don maganin layin farko ana ɗaukar shi a halin yanzu.
Hakanan ana bincikar haɗin kai tsakanin masu hana wuraren bincike na rigakafi da hanyoyin kwantar da hankali na gida (ciki har da zubar da jini, jiyya na radiation da chemoembolization transarterial (TACE)). Ciwon daji tare da ƙananan nauyin maye gurbi da ƙananan sabbin antigens gabaɗaya ba su da ƙarancin rigakafi kuma ba su da / ƙarancin amsa (ko juriya na farko) ga masu hana wuraren bincike. Jiyya na gida da maganin radiation suna haifar da kumburi da kuma samar da sababbin antigens waɗanda aka saki a cikin jini. Sabili da haka, ana sa ran haɗuwa da masu hana wuraren bincike da kuma maganin yanki na gida don ƙara yawan hankali ga masu hana wuraren bincike.
A cikin binciken farko na marasa lafiya 32, an yi amfani da temlimumab (tremelimumab) tare da ablation na mitar rediyo ko TACE. Ana lura da halayen ɓangarori a cikin har zuwa 25% na marasa lafiya.
Sashen likitancin Global Oncologist Network na likitanci ya lissafa gwaji na asibiti na yanzu game da maganin hana yaduwar rigakafi da maganin hadewa a teburin mai zuwa don tunatarwar ku. Waɗanda ke son shiga za su iya kiran sashen kiwon lafiya don kimantawa na farko.
Maganin rigakafi na rigakafi
CAR-T SARA TARIHI
T cells engineered with chimeric antigen receptors (CAR) gain the ability to recognize certain antigens, which allows specific cells (including tumo 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 cell far
NK (kwayar cutar kisa, NK) ita ce ƙwayar rigakafi tare da mafi ƙarfi tasirin cutar kansar. Wuri mafi ƙarfi shine cewa zai iya kai tsaye da sauri baƙuwar jikin ƙasashen waje (ƙwayoyin cuta da ƙwayoyin cuta) ba tare da aiwatar da gabatarwar antigen ba tare da wasu mutane sun ba da rahoto ba. Sel, ƙwayoyin kansa, ƙwayoyin rai, da sauransu)
Kwayoyin NK, kamar “Sarkar Kwayoyin Halitta”, suna sintiri cikin jini. Da zarar sun sami kwayoyin halitta na waje ko kwayoyin rikirkita wadanda suka rasa ganewarsu (wanda ake kira MHC), nan take mai karɓar kwayar ta NK zai aika da sigina kuma ya hanzarta zuwa membrane ɗin da ake so. Wato, kwayoyin NK dole ne su kasance a layin gaba na yaƙi. Yana fitar da kwayoyi masu guba a gare shi, da sauri ya narkar da kwayoyin halitta, kuma ya sa kwayoyin cutar kansar su mutu cikin minti 5.
Ya kamata a sani cewa kwayoyin NK, a matsayin ainihin ɓangaren tsarin garkuwar jiki, sune mahimman ƙwayoyin ƙwayoyin cuta masu haɓaka a jikin mutum, amma suna da ƙarancin gaske a cikin jinin jikin mutum, wanda yakai 5% -10% na lymphocytes kawai. Kwayoyin suna lissafin 30-50% na lymphocytes a cikin hanta hanta mutum. Idan aka kwatanta da kewaya ƙwayoyin NK, ƙwayoyin NK a cikin hanta suna da halaye masu ban mamaki da halaye na aiki, suna nuna mafi girman ƙwayar cuta zuwa ƙwayoyin ƙari. Yayin faruwar cutar sankarar hanta, an rage adadin kwayoyin NK da aikin cytokine (interferon-γ) da aikin cytotoxic. Sabili da haka, hanyoyin kwantar da hankali waɗanda ke sake kunna ƙwayoyin NK da amfani da su don kai farmaki ga ciwace-ciwacen haɗi
ude chemoimmunotherapy da dashen dashen kwayoyin NK. A halin yanzu akwai gwaji na zamani na I / II na gwaji na 7 wanda ke bincikar rigakafin rigakafin ƙwayoyin NK a cikin marasa lafiyar HCC, mafi yawansu suna ɗaukar rikodin rikodin na autologous ko allogeneic NK.
Maganin 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.
Nazarin farko na nazarin marasa lafiya 33 tare da HCC mai ci gaba ta amfani da allurar rigakafin GPC3 peptide ya nuna cewa an yi haƙuri da allurar rigakafin, mai haƙuri 1 yana da gafara na ɓangare (3%), kuma marasa lafiya 19 suna da cuta mai ƙarfi a watanni 2 (58%). Kashi 3 cikin dari na marasa lafiya sun haɓaka amsar kwayar lymphocyte T ta cytotoxic bayan shigar da su tare da takamaiman rigakafin GPC3, wanda ke da alaƙa da rayuwa gabaɗaya. Haɗin amfani da maganin GPCXNUMX peptide da sauran hanyoyin kwantar da hankali a halin yanzu ana ci gaba da bincika su.
Kalmomi ga marasa lafiyar kansar hanta
Mun shiga wani sabon zamani a cikin maganin ciwon daji na hepatocellular, wanda dabarun da suka dogara da masu hana shinge na rigakafi ba da daɗewa ba za su zama tushe, ko dai a matsayin monotherapy ko a hade tare da sauran masu hanawa da kuma kinase inhibitors. Bugu da ƙari, sabon bincike na Immunotherapy da ci gaba ya kuma kawo ƙarin bege da zaɓuɓɓukan magani ga marasa lafiya masu ci gaba. Saboda akwai gwaji na asibiti da yawa, ba zai yiwu a gabatar da su ɗaya bayan ɗaya a cikin wannan labarin ba.
