Dandalin Ci Gaban Magungunan Hana Cututtukan Bispecific

Alpha Lifetech na iya samar wa abokan ciniki ingantattun gano ƙwayoyin cuta masu inganci da kuma samfuran furotin da ayyukan sake haɗawa. Za mu iya shirya ƙwayoyin cuta masu inganci, takamaiman aiki, da kuma kyakkyawan kwanciyar hankali. Alpha Lifetech tana da nau'ikan kayan aikin tsarkake ƙwayoyin cuta iri-iri, waɗanda za su iya samar da ayyukan tsarkake ƙwayoyin cuta daga tushe daban-daban kamar zomo, tumaki, kaza, da linzamin kwamfuta, da kuma ayyukan tsarkake ƙwayoyin cuta masu alaƙa da furotin A/G da kuma ayyukan tsarkake ƙwayoyin cuta da tsarkake ƙwayoyin cuta. Dangane da cikakken tsarin dandamali na gina dandamalin gano ƙwayoyin cuta, dandamalin furotin, da sauransu, muna rufe ayyukan samar da ƙwayoyin cuta masu alaƙa da sama da ƙasa, kuma za mu iya samar da ayyukan fasaha daga shirye-shiryen ƙwayoyin cuta, tsarkake ƙwayoyin cuta masu alaƙa da juna da kuma rabuwa da ƙwayoyin cuta masu alaƙa da ƙwayoyin cuta, jerin ƙwayoyin cuta masu alaƙa da ƙwayoyin cuta, tabbatar da ƙwayoyin cuta masu alaƙa da ƙwayoyin cuta, da sauransu,, waɗanda za a iya amfani da su don maganin ƙwayoyin cuta masu alaƙa da juna.

Kwayoyin rigakafi na monoclonal suna nufin immunoglobulins da aka samar ta hanyar ƙwayar B guda ɗaya wacce ke da takamaiman takamaiman ƙwayoyin cuta ko epitopes. An fara shirya samar da ƙwayoyin rigakafi na monoclonal ta amfani da fasahar hybridoma don samar da ƙwayoyin rigakafi na linzamin kwamfuta. Musamman, ta hanyar haɗa ƙwayoyin spleen daga beraye da aka yi wa rigakafi tare da ƙwayoyin myeloma daga mutane ko beraye, ana samar da ƙwayoyin rigakafi na hybridoma, waɗanda ke fitar da takamaiman ƙwayoyin rigakafi. Kwayoyin rigakafi na monoclonal na linzamin kwamfuta da aka samar galibi ana amfani da su ne a binciken dabbobi da kuma gano cututtuka bayan ayyukan tsarkakewa. Duk da haka, jikin ɗan adam zai samar da martanin rigakafi ga sunadaran linzamin kwamfuta na ƙasashen waje, don haka akwai ƙuntatawa mai mahimmanci a cikin amfani da asibiti na samar da ƙwayoyin rigakafi na monoclonal na linzamin kwamfuta. Daga baya, mutane sun yi amfani da "humanization" don shirya ƙwayoyin rigakafi na monoclonal daga beraye, kuma sun yi amfani da fasahar injiniyan kwayoyin halitta don gyara ƙwayoyin rigakafi na linzamin kwamfuta don samun yankin immunoglobulin na ɗan adam akai-akai don rage ƙarfin garkuwar jiki. Wannan nau'in ƙwayoyin rigakafi kuma ana kiransa da ƙwayoyin rigakafi na monoclonal na ɗan adam. Bugu da ƙari, amfani da ƙwayoyin halitta na ɗan adam don samar da ƙwayoyin rigakafi na monoclonal na ɗan adam ana kiransa shirye-shiryen ƙwayoyin rigakafi na monoclonal na ɗan adam gaba ɗaya. Ana amfani da ƙwayoyin rigakafi na monoclonal sosai a aikace-aikacen likitanci da na asibiti. A binciken likitanci, ana iya amfani da ƙwayoyin rigakafi na monoclonal a matsayin immunomodulators, ana iya amfani da ƙwayoyin rigakafi na monoclonal don maganin cutar kansa da kuma maganin kamuwa da cutar ta hanyar ƙwayoyin cuta, kuma ana amfani da ƙwayoyin rigakafi na monoclonal conjugates galibi don maganin cutar kansa.

Gabatarwa ga Maganin Hana ...

A shekarar 1960, an gabatar da manufar ƙwayoyin rigakafi na bispecific. Kwayoyin rigakafi na bispecific, waɗanda aka fi sani da ƙwayoyin rigakafi na monoclonal bispecific, ƙwayoyin rigakafi ne da aka haɗa ta hanyar amfani da fasahar injiniyan kwayoyin halitta. A matsayinsu na ƙwayoyin rigakafi na wucin gadi, ƙwayoyin rigakafi na bispecific galibi suna cikin ƙaramin aji na IgG kuma suna ɗauke da guntu mai ɗaure antigen wanda ke niyya ga ƙaramin CD3. Kwayoyin rigakafi na bispecific suna da takamaiman wuraren ɗaure antigen guda biyu waɗanda zasu iya ɗaurewa da gane antigens guda biyu daban-daban a lokaci guda, ko epitopes guda biyu daban-daban na wani antigen. Idan aka kwatanta da ƙwayoyin rigakafi na monoclonal, ƙwayoyin rigakafi na bispecific suna da ƙarin takamaiman wurin ɗaure antigen, don haka suna da ƙarfi na musamman da ikon niyya, wanda zai iya kai hari ga ƙwayoyin ƙari daidai da kuma rage gubar da aka yi niyya. Kwayoyin rigakafi na bispecific na iya yin ayyuka da yawa na halitta a lokaci guda, kamar ɗaukar ƙwayoyin rigakafi, toshe hanyoyin sigina, da kashe ƙwayoyin ƙari kai tsaye. Kwayoyin rigakafi na bispecific na farko an shirya su ne ta hanyar haɗa sinadarai ko haɗakar ƙwayoyin halitta, amma wannan hanyar na iya ci gaba a hankali saboda haɗuwa bazuwar da wahalar ware haɗin da aka yi niyya. Tare da ci gaba da haɓaka fasahar injiniyan kwayoyin halitta, an ƙirƙiri sabbin dandamali na fasaha da yawa, kamar knots in holes (KIH), CrossMab, DVD Ig, da sauransu. Waɗannan dandamali suna magance matsaloli kamar rashin daidaiton sarka mai nauyi da sarka mai sauƙi yadda ya kamata, kuma suna inganta daidaito da yawan ƙwayoyin rigakafi na bispecific.

Hoto na 1. Bayani mai sauƙi game da hanyoyin da aka tsara na aiki ga ƙwayoyin rigakafi na bispecific (bsAbs) a cikin gwaje-gwajen asibiti don cutar kansa.(Tushen hoto: Bita kan ƙwayoyin rigakafi na bispecific da tsarin ƙwayoyin rigakafi a cikin oncology da ƙalubalen asibiti - ScienceDirect)

Fasahar Samar da Kwayoyin Hana ...

Manyan hanyoyin samar da ƙwayoyin cuta masu alaƙa da bispecific sun haɗa da haɗin sinadarai, hybridoma mai tushe huɗu, da kuma shirye-shiryen ƙwayoyin cuta na injiniyan kwayoyin halitta. Daga cikinsu, hanyar haɗa sinadarai tana haɗa gutsuttsuran ƙwayoyin cuta guda biyu na IgG ko F (ab ') guda biyu zuwa ga ƙwayoyin cuta masu alaƙa da bispecific ta amfani da sinadaran haɗin sinadarai kamar phthalimide da dithioacylbenzoic acid. Wannan hanya ce mai sauƙi kuma mai sauƙin aiki, amma tana iya lalata wurin ɗaure antigen, rage ayyukan ƙwayoyin cuta, kuma wakilin haɗin kanta shi ma yana da wani matakin cutar kansa. Hanyar hybridoma mai tushe huɗu ta dogara ne akan haɗa ƙwayoyin cuta masu alaƙa da layukan ƙwayoyin cuta guda biyu daban-daban don bayyana linzamin kwamfuta IgG mai dacewa. Ta hanyar fasahar injiniyan kwayoyin halitta, ana iya canza ƙwayoyin cuta ta hanyar halitta don samar da ƙwayoyin cuta masu alaƙa da bispecific. An gina ƙwayoyin cuta guda biyu daban-daban na monoclonal, kuma an raba gutsuttsuran Fab ko yankuna masu canzawa na sarkar nauyi da sarkar haske na ƙwayoyin cuta guda biyu daban-daban. Ta hanyar haɗa haɗin gwiwa ko fasahar haɗa sarkar, an haɗa gutsuttsuran guda biyu don samar da ƙwayoyin cuta masu alaƙa da bispecific. Kodayake sarkakiyar fasahar injiniyan kwayoyin halitta tana da yawa, a halin yanzu ita ce hanyar da aka fi amfani da ita don samar da ƙwayoyin cuta masu alaƙa da bispecific don daidaita tsarin da aikin ƙwayoyin cuta. Lokacin gudanar da ƙirar rigakafi ta bispecific, ana iya amfani da ƙa'idar amsawar rigakafi ta hanyar haɗin gwiwa, amma amsawar rigakafi ta hanyar haɗin gwiwa na iya haifar da amsawar da ba ta da takamaiman takamaiman, don haka za a yi la'akari da shi sosai a aikace a cikin amfani da ƙirar rigakafi ta bispecific, kamar maganin rigakafi ta bispecific.

Tsarkakewar Kwayoyin Hana Kwayoyin Hana Bispecific

Tsarkakewar ƙwayoyin cuta ta Bispecific ita ce hanyar ware da tsarkake ƙwayoyin cuta masu ƙarfi. Ana amfani da hanyoyi guda biyu, centrifugation da kuma zurfin tacewa, don cire wasu ƙazanta masu narkewa. Da farko ana kama ƙwayar cuta ta Bispecific ta hanyar amfani da chromatography na affinity. Ga ƙwayoyin cuta kamar bispecific IgG, ana amfani da chromatography na affinity na furotin A, yayin da ga ƙwayoyin cuta marasa IgG kamar bispecific, ana iya amfani da chromatography na affinity bisa sarkar haske. Bayan haka, ana sanya ƙwayar cuta a cikin ƙananan yanayin pH na wani lokaci, wanda ke haifar da rushewar tsarin furotin a saman ƙwayar cuta, don haka yana rasa ikon kamuwa da ƙwayoyin cuta. Ana yin tacewa mai zurfi na matsakaici don ƙara cire ƙazanta kamar furotin na ƙwayoyin cuta (HCP). Ana inganta tsarkin ƙwayoyin cuta ta hanyar hanyoyin kamar chromatography na musayar ion, kuma ana cire duk wani ƙwayar cuta da ya rage ta hanyar dabarun nanofiltration ko ultrafiltration. A ƙarshe, ana tattara samfurin kuma ana maye gurbinsa da ingantaccen tsari mai kariya.

Tsarin Aikin Samar da Magungunan Kariya na Bispecific

Matakai	Abubuwan Sabis	Tsarin lokaci
Tsarin Halitta	Samar da har zuwa tsare-tsaren zane guda uku daban-daban na jerin, tun daga farkon samar da ƙwayoyin halittar DNA na ƙwayoyin halittar rigakafi masu sake haɗawa	Makonni 2-3
Gwajin Ƙaramin Sikeli	Samar da sunadaran rigakafi na bispecific → Ƙaramin siffa a cikin layukan ƙwayoyin dabbobi masu shayarwa → Tabbatarwa ta SDS-PAGE → Binciken ɗaurewa tare da antigens na furotin masu sake haɗawa ta ELISA → Kwatanta kwafi da ƙwayoyin rigakafi na iyaye	Makonni 5-6
Gano	Bayyanar ƙwayoyin rigakafi guda biyu na farko masu tsayin bispecific → Binciken ɗaurewa ta ELISA → Kimantawar ELISA na ƙwayoyin rigakafi da aka gane ta hanyar ƙwayoyin rigakafi na linzamin kwamfuta	Mako 1
Samar da Maganin Cututtuka	Samar da babban matakin rigakafi	Makonni 3-4

Amfaninmu

Muna kula da ayyukan samar da rigakafi daga sama zuwa ƙasa, kuma muna iya samar da ayyukan fasaha daga shirye-shiryen rigakafi, tsarkake rigakafi daga bispecific da rabuwa da tsarkake rigakafi, jerin kwayoyin cuta, tabbatar da rigakafi daga ƙwayoyin cuta, da sauransu, waɗanda za a iya amfani da su don maganin rigakafi daga bispecific.

Babban Ma'ana

Yawan furotin a cikin ƙwayoyin CHO.
Ajiya Mai Tsayi

Makonni 2 a cikin jini a zafin jiki na 37 ° C.
Babu Matsalar Rage Narkewa

>30 mg/ml
Layin Kwayoyin Zamani Mai Sauƙi

An ƙirƙiro layukan ƙwayoyin halitta masu ƙarfi da yawa tare da ƙwayoyin cuta masu cutar kansa don tabbatar da yawancin ƙwayoyin rigakafi na bispecific