Immunotherapy yana amfani da kwayoyi don taimakawa tsarin garkuwar jiki da kyau don gane da lalata ƙwayoyin cutar kansa. Ana iya amfani da immunotherapy don kula da marasa lafiya da ciwon daji mai ci gaba.
Mai hana shigowar shinge
Wani muhimmin bangare na tsarin garkuwar jiki shine karfinta na kare kansa daga afkawa cikin kwayoyin halittar jikin mutum. Saboda wannan, yana amfani da sunadaran “checkpoint” akan ƙwayoyin rigakafi, waɗanda suke aiki kamar masu sauyawa waɗanda suke buƙatar kunna (ko kashe) don fara amsar garkuwar jiki.
Kwayoyin cutar kansa wasu lokuta suna amfani da waɗannan wuraren binciken don dakatar da tsarin rigakafi daga afka musu. Koyaya, magungunan da aka yi niyya akan waɗannan wuraren binciken suna da kyakkyawan fata kamar hanyoyin maganin kansar.
Ana iya amfani da ƙwayoyi da ake kira masu hana shingen bincike a cikin mutanen da ƙwayoyin cutar kansa ke gwada tabbatacce ga takamaiman canjin halittar, kamar su mawuyacin halin rashin aikin microsatellite (MSI-H), ko ɗaya daga cikin nau'ikan gyare-gyaren rashin daidaito (MMR) Canjin yanayi.
Ana amfani da waɗannan magungunan a cikin mutanen da ciwon daji ke ci gaba da girma bayan chemotherapy. Hakanan ana iya amfani da su don kula da mutanen da ba za a iya kawar da cutar kansa ta hanyar tiyata ba, sake dawowa bayan jiyya (sake dawowa) ko ya yadu zuwa wasu sassan jiki (metastasis).
Amintattun magungunan rigakafi
An amince da mai hana PD-1
Pembrolizumab (Pembrolizumab, Keytruda) da nivolumab (Nivolumab, Opdivo) kwayoyi ne da ke kaiwa ga PD-1, furotin da ke kan sel na tsarin garkuwar jiki da ake kira T cell wanda yawanci ke taimakawa Hana waɗannan ƙwayoyin cuta daga kai hari ga sauran ƙwayoyin jikin. Ta hanyar toshe PD-1, waɗannan magungunan na iya haɓaka amsawar rigakafi ga ƙwayoyin cutar kansa.
A ranar 24 ga Mayu, 2017, FDA ta Amurka ta amince da PD-1 mai hanawa pembrolizumab (Pembrolizumab, Keytruda) don kula da marasa lafiya masu ciwon daji tare da microsatellite sosai m (MSI-H) / rashin daidaituwa gyara lahani (dMMR), The ƙari iri rufe 15 daban-daban m ciwace-ciwacen daji, ciki har da colorectal cancer, kananan cell huhu ciwon daji, da kuma mahaifa.
A ranar 2 ga Agusta, 2017, Hukumar Abinci da Magunguna ta Amurka (FDA) ta amince da nivolumab (Navumab, Opdivo) don maganin fluorouracil, oxaliplatin, da irinotecan. Microsatelite tare da rashin ƙarfi sosai (MSI -H) Jiyya na cututtukan cututtukan cikin gida na manya ko yara (≥12 shekara) ko kuskuren gyara kuskure (dMMR).
An yarda da mai hana CTLA-4
Ipilimumab (Yervoy) wani magani ne wanda zai iya inganta haɓakar rigakafi. Ba za a iya amfani da shi shi kaɗai ba. Yana buƙatar haɗuwa da nivolumab, wanda ke toshe CTLA-4, wanda shine wani furotin akan ƙwayoyin T.
Shari'ar nasara ta MSI-High (MSI-High) mCRC ita ce amfani da haɗin gwiwa na nivolumab da ipilimumab, wanda aka kimanta a cikin binciken na Phase II CheckMate142. Haɗin haɗin haɗin ya nuna ORR (ƙimar amsawar haƙiƙa) na 49%, kuma 5 na marasa lafiya 119 suna da CR (cikakkiyar amsa) da 53 PR (amsa na wani ɓangare). Yawancin marasa lafiya (n = 82) a baya sun karɓi fluorouracil, oxaliplatin da irinotecan. A cikin waɗannan marasa lafiya, ORR ya kasance 46%, 3 CRs da 35 PRs.
Dangane da bayanan CheckMate-142, FDA ta amince da haɗin (Nivolumab + Ipilimumab) don kula da manya da yara na yara masu shekaru 12 zuwa sama, gami da marasa lafiyar mCRC da ke da MSI-H ko rashin gyara matsala (dMMR), Waɗannan marasa lafiya sun ci gaba bayan jiyya da fluorouracil, oxaliplatin da irinotecan.
Fassarar aikace-aikacen MSI / dMMR a cikin maganin launi
MSI tana nufin asarar ƙwayoyin halittun da ba su dace ba wanda ya haifar da methylation na DNA ko maye gurbi, wanda ke haifar da canje-canje a cikin tsayin bayanan maimaita microsatellite. Binciken ya gano cewa MSI-H muhimmiyar alama ce ta biomarker don ciwace-ciwacen da suka dace da rigakafin rigakafi.
MSI rashin daidaiton microsatellite ne, MMR (gyaran ba daidai ba) yana nufin aikin gyara rashin daidaiton kwayar halitta. Kwayar halittar mutum ta gyara rashin daidaituwa (kwayar MMR) na iya bayyana daidaitaccen furotin gyaran bayan rubutaccen fassara da fassara. Idan asarar magana ta kowane furotin na MMR na iya haifar da lahani a cikin aikin gyara rashin daidaiton kwayar, rashin daidaiton tushe kan aiwatar da kwafin DNA Asarar aikin gyara yana haifar da tarawa, wanda ke haifar da faruwar rashin daidaiton microsatellite (MSI). Kimanin 15% na cututtukan daji na launi suna haifar da hanyar MSI.
Ana iya amfani da PCR don gano tsawon shafukan yanar gizo na microsatellite (microsatellites su ne tandem maimaitawa na gajerun jerin DNA a cikin kwayoyin halittar eukaryotes) a cikin DNA cell tumor, sa'an nan kuma idan aka kwatanta da DNA tantanin halitta daidai. Tare da yaɗawa da aikace-aikacen NGS (Second Generation Sequencing), ban da maganin rigakafi na gargajiya da gano PCR, ana iya gano matsayin microsatellite akan dandalin NGS. Don fahimtar cibiyoyin gwajin kwayoyin halittar NGS masu iko a gida da waje, da fatan za a tuntuɓi 400-626-9916.
Bugu da ƙari, ana iya amfani da nau'o'in ƙwayoyin cuta (ciki har da na tiyata da na hudawa) don gano ƙwayoyin cuta na ƙwayoyin cuta guda huɗu, waɗanda suka haɗa da: MLH1, MSH2, MSH6, da PMS2. Duk lokacin da ɗayan waɗannan sunadarai suka ɓace, ƙari yana cikin dMMR, wanda ke da nakasa a aikin gyara rashin daidaituwa. Idan duk sunadarai huɗu sun bayyana da kyau kuma ƙari shine pMMR, aikin gyara rashin daidaituwa ya cika.
Nazarin jigilar kwayoyin halittar MSI
Hoton da ke gaba yana nuna mai haƙuri daga Global Oncologist Network wanda aka gano yana da MSI-H bayan gwajin MSI ta kamfanin gwajin ƙwayoyin gida (400-626-9916). Wannan mai haƙuri yana da sa'a sosai kuma ya dace da immunotherapy.
Wani mai haƙuri a kan Cibiyar Harkokin Oncologist na Duniya an gwada shi da kyau ta Amurka Keruis Gene (400-626-9916), kuma dukkanin sunadaran guda huɗu sun kasance tabbatacce (tabbatacce), wanda ke nufin cewa mai haƙuri ya kasance pMMR, kuma bai dace da Immunotherapy da aka yarda da shi a sama ba .
Fassarar sakamakon gwaji na ƙarshe za a iya raba shi zuwa MSS (kwanciyar hankali na microsatellite), MSI-L (microsatellite low instability) da MSI-H (microsatellite high instability). Gabaɗaya, dMMR yayi daidai da MSI-H, kuma pMMR yayi daidai da MSS da MSI-L.
Kariya don amfani da masu hanawa na PD-1
- Ana ba da waɗannan ƙwayoyin azaman ƙwayoyin cuta na intravenous (IV) kowane mako 2 ko 3.
- Illolin wadannan magunguna sun haɗa da gajiya, tari, tashin zuciya, ƙaiƙayi, kumburi, rashi cin abinci, maƙarƙashiya, ciwon haɗin gwiwa da gudawa.
- Sauran cututtukan da suka fi tsanani suna faruwa sau da yawa. Lokaci-lokaci, tsarin garkuwar jiki na iya kai farmaki ga wasu sassan, mai yuwuwa ya haifar da matsaloli masu haɗari ko barazanar rai a cikin huhu, hanji, hanta, gland, hormone, kodan, ko wasu gabobin.
- A lokacin jiko, yanayin lafiyar mai haƙuri yana buƙatar kulawa a ainihin lokacin.
Kariyar maganin Ipilimumab
- Ana amfani da wannan maganin tare da nivolumab (Opdivo) don magance kansar kai tsaye, amma ba za a iya amfani da shi shi kaɗai ba. Ana gudanar da shi ta hanyar jigilar jini (IV), yawanci kowane sati 3 don zagayowar magani 4.
- Illolin dake tattare da wannan maganin sun hada da kasala, gudawa, kumburi da kaikayi.
- Lokacin amfani da wannan magani, illolin haɗari masu tsanani kamar sun zama gama gari fiye da amfani da masu hana PD-1. Kamar masu hanawa na PD-1, wannan magani na iya haifar da tsarin garkuwar jiki da kai farmaki ga wasu sassan jiki, wanda zai iya haifar da matsala mai tsanani tare da hanji, hanta, glandan da ke samar da hormone, jijiyoyi, fata, idanu, ko wasu gabobin. A wasu mutane, waɗannan illolin na iya zama barazanar rai.
- A lokacin jiko, yanayin lafiyar mai haƙuri yana buƙatar kulawa a ainihin lokacin.
Yadda za a zabi magungunan rigakafi a cikin sankarar sankarau?
Baƙon Ba'amurke masanin kansar kwarkwata Dr. Chiorean ya ce, “Pembrolizumab ko nivolumab sun fi son marasa lafiya da MSI-H. Nivolumab haɗe tare da ipilimumab (mai hana CTLA-4) da wuya ake amfani da shi. Ina tsammanin bambancin i
s very small. Similarly, some people may argue that CTLA-4 may be better tolerated by the inhibitory response, but I also feel that the toxicity is significantly higher. ”
Dr. Messersmith said that when he needed to quickly obtain therapeutic effects, he used nivolumab and ipilimumab combination therapy. Adding ipilimumab can get an additional 15%–20% response rate. If the patient is symptomatic, it can be added. Even though this may increase adverse reactions, the treatment effect is even greater. This requires an assessment of the patient’s physical condition.
If patients and their families have difficulty in choosing an immunotherapy drug, they can seek domestic authoritative colorectal cancer experts for consultation through the Global Oncologist Network (+91 96 1588 1588) to determine the final, more suitable treatment plan.
