Cov nyhuv ntawm interleukin ntawm kev ua haujlwm ntawm NK hlwb (IL-1β, IL-12, IL-15, IL-18, IL-21)
Tau qhov twg los: T&L Biotechnology Tso Tawm Sijhawm: 2023-08-24
Ntuj killer cells yog los ntawm cov pob txha pob txha lymphoid Stem Cells thiab yog innate immune effector cells hauv lub cev. Lawv muaj npe tom qab lawv tsis yog tshwj xeeb cytotoxicity. Kev tua ntawm NK hlwb tsis txwv los ntawm MHC thiab tsis nyob ntawm cov tshuaj tiv thaiv, yog li nws yog hu ua natural killing act. Nws tua cov qog hlwb los ntawm kev sib cais ncaj qha thiab tso tawm ntawm cytokines, ua rau txoj kev loj hlob ntawm nws cov tshuaj tiv thaiv kab mob ua haujlwm yog lub ntsiab lus kub hauv kev tshawb fawb txog qog noj ntshav hauv xyoo tas los no.
Interleukins yog ib pawg ntawm cytokines zais cia los ntawm ntau hom hlwb uas tuaj yeem tswj hwm kev loj hlob ntawm tes, sib txawv, thiab kev tiv thaiv kab mob. Lawv feem ntau cuam tshuam nrog NK hlwb, lossis ncaj qha koom nrog kev tswj hwm ntawm NK hlwb, lossis tsis ncaj qha tswj kev ua haujlwm ntawm NK hlwb los ntawm kev cuam tshuam rau lwm lub hlwb. Interleukins xws li IL-2, IL-15, thiab IL-18 yog suav hais tias yog yam uas txhawb nqa NK hlwb thiab siv rau hauv vitro nthuav dav ntawm NK hlwb. Lawv muaj kev tswj hwm zoo ntawm kev ua kom thiab sib txawv ntawm NK hlwb. Qhov sib ntxiv ntawm cov cytokines thaum lub sij hawm hauv vitro kab lis kev cai tuaj yeem txhim kho kev tua ntawm NK hlwb.1, Txhawb nqa NK cell expansion thiab ua kom muaj zog: IL-2/21
Txij xyoo 1996, Soffer RJ li al. muaj rRojrted hais tias kev txhaj tshuaj tsis tu ncua thiab kev tswj xyuas tsis tu ncua ntawm IL-2 muaj qhov cuam tshuam loj rau CD56 + NK hlwb hauv cov neeg mob uas mob qog noj ntshav. Feem ntau NK hlwb muaj affinity receptors rau IL-2 ntawm lawv qhov chaw, thiab IL-2 induces NK cytotoxicity nyob rau hauv kwv yees li 18-24 teev. Tsis tas li ntawd, IL-2 tuaj yeem ua rau muaj kev loj hlob ntawm NK hlwb, uas feem ntau pib 3-4 hnub tom qab stimulation. Lub tshuab yog tias IL-2 tuaj yeem ua rau muaj kev qhia ntawm IL-2R hauv NK hlwb α Chain, qhia tshiab α Chain thiab thawj cell nto β Chain thiab γ Chain binding cov ntaub ntawv siab affinity receptors, uas txhawb nqa NK cell proliferation nyob rau hauv lub xub ntiag ntawm IL-2.
Duab Source: Sharma R, et al. Immunol Res. 2018
Wendt K et al. tau tshaj tawm tias hauv kev tswj hwm ntawm NK cell muaj nuj nqi, IL-2 ib leeg tuaj yeem txhawb kev nthuav dav ntawm tib neeg NK hlwb, thaum kev sib xyaw ntawm IL-2 thiab IL-21 ua rau muaj kev nthuav dav ntxiv.
Li Q et al. tau tshaj tawm tias IL-21 muaj qhov cuam tshuam loj heev rau tib neeg NK hlwb kab lis kev cai hauv vitro, nrog rau kev nce ntxiv ntawm cov xov tooj ntawm tes. Nws kuj txhawb kev nthuav dav ntawm cov hlwb mus rau theem S ntawm lub voj voog ntawm tes thaum thawj ob lub lis piam ntawm kab lis kev cai. Nws kuj txhawb cov hlwb kom nkag mus rau theem S ntawm lub voj voog ntawm tes thaum thawj zaug mus rau lub lim tiam thib ob ntawm kev cog qoob loo.
Duab Source: Li Q, et al. Immunobiology. 2015.
2.Inducing sib txawv ntawm NK hlwb: IL-1β/ 12/15
Lub cev tiv thaiv kab mob phenotype ntawm NK hlwb yog CD3-CD56+, thiab tam sim no feem ntau ntseeg tias lawv sib txawv ncaj qha los ntawm cov pob txha pob txha hematopoietic qia hlwb, uas yog, los ntawm CD34 + hematopoietic qia hlwb. Ntau qhov kev sim tau lees paub tias CD34 + cell muab tau los ntawm cov pob txha pob txha tuaj yeem sib txawv rau hauv NK hlwb hauv vitro los ntawm cytokine induction, muab lwm txoj hauv kev rau lub hauv paus ntawm NK hlwb.
Ambrosini et al. txheeb xyuas cov txiaj ntsig ntawm IL-1β ntawm qhov sib txawv ntawm NK hlwb los ntawm cov hlab ntsha hlab ntsha CD34 + precursor hlwb, thiab cov ntaub ntawv qhia tias IL-1β inhibits ILC3 thaum txhawb kev loj hlob ntawm cov hlab ntsha hlab ntsha CD34 + precursor NK hlwb.
Li Yan et al. ua nyob rau hauv vitro induction sib txawv thwmsim ntawm CD34 + leukemia hlwb muab tau los ntawm cov pob txha pob txha ntawm cov neeg mob uas mob myeloid leukemia. CD34 + leukemia hlwb tuaj yeem raug ntxias kom sib txawv rau hauv NK hlwb hauv vitro uas muaj cov haujlwm cytotoxic. Kev sib xyaw ua ke ntawm IL-12 thiab 1L-15 cytokines tuaj yeem ua rau muaj kev sib txawv ntawm NK cell kev ua haujlwm, txhim kho kev tua tus nqi ntawm leukemia hlwb thiab qhia qib ntawm TNF-α thiab IFN-γ noob.
Duab Source: Li Yan et al. Phau ntawv Journal of Clinical Oncology, 2019
3. Txhim kho NK cell toxicity: IL-12/18/21
Guia et al. pom tias nyob rau hauv cov neeg mob uas tsis muaj peev xwm ua tiav ntawm IL-12Rbeta1 tshwm sim los ntawm IL12RB1 kev hloov pauv, NK cell subpopulation tau txo qis, tshwj xeeb tshaj yog hauv kev tsim cov IFN-γ; Cov ntaub ntawv zoo sib xws tau txais los ntawm cov neeg mob uas tau ua tiav ntawm IL-12p40. Tsis tas li ntawd, tus naj npawb ntawm effector nco T cell subpopulation qhia CD56 tau txo qis hauv cov neeg mob IL-12Rbeta1 thiab IL-12p40 deficiency. Yog li ntawd, tib neeg NK hlwb xav tau IL-12 hauv vivo kom tau txais nws cov spectrum tag nrho ntawm kev ua haujlwm.
Duab qhov chaw: Guia S, et al. Ntshav. Xyoo 2008
Mirjačić et al. tshawb xyuas cov teebmeem ntawm IL-12 thiab IL-18 ntawm kev ua haujlwm thiab receptor yam ntxwv ntawm NK hlwb thiab lawv cov subsets hauv cov neeg mob metastatic melanoma. Kev sib xyaw ua ke ntawm IL-12 thiab IL-18 hauv vitro tuaj yeem tsim cov txiaj ntsig zoo ntawm NK cell toxicity thiab CD25 receptor qhia hauv cov neeg mob metastatic melanoma.
Duab qhov chaw: Mirjačić et al.. J Transl Med. 2015. PIB: 25889680.
Strengell M et al. kuj tau tshaj tawm tias cov nyhuv synergistic ntawm IL-21 nrog IL-15 lossis IL-18 tuaj yeem txhim kho kev tsim cov IFN-γ hauv tib neeg NK thiab T hlwb, ua rau muaj kev cuam tshuam cytotoxic.
Duab qhov chaw: Strengell M, et al. J Immunol. Xyoo 2003.
Beijing T&L Biotechnology Ltd., tau tsom mus rau R&D thiab tsim khoom ntawm GMP qib core reagent raw cov ntaub ntawv hauv CGT teb rau ntau tshaj kaum xyoo, thiab muab kev daws teeb meem rau kev ua neej nyob. Lub tuam txhab muaj eukaryotic thiab prokaryotic protein qhia engineering platforms, cell culture technology development platforms, thiab in vitro diagnostic reagent ntau lawm platforms. GMP qib recombinant protein tsim muaj cov yam ntxwv ntawm qis endotoxin, siab purity, siab ua haujlwm, thiab siab interbatch sib xws. Nyob rau tib lub sijhawm, cov khoom siv dawb huv ntawm tes kab lis kev cai reagent muab muaj kev ua kom zoo thiab nthuav dav thiab ua haujlwm ua haujlwm. Tam sim no, lub tuam txhab cov khoom tseem ceeb raw khoom xws li recombinant protein thiab cell kab lis kev cai reagent cov khoom siv ntau lawm kab tau ua tiav FDA DMF filing, uas yuav ua tau raws li cov kev xav tau ntawm cov neeg siv xov tooj ntawm tes tshaj tawm tshuaj.
T&L pom zoo NK cell culture khoom:
1. NK Culture Key Proteins: Recombinant human IL-1β protein
Fig1: Recombinant Tib Neeg IL-1β txhawb nqa kev tso tawm ntawm IFN-γ los ntawm NK-92 tib neeg lub cev tua cov qog ntshav qog ntshav
Recombinant human IL-12 protein
Fig2: Recombinant Tib Neeg IL-12 txhawb nqa kev loj hlob ntawm PBMC
Recombinant human IL-15 protein
Fig3: Recombinant Tib Neeg IL-15 txhawb kev loj hlob ntawm CTLL-2
Recombinant human IL-18 protein
Fig4: Recombinant Tib Neeg IL-18 txhawb nqa kev loj hlob ntawm KG-1
Recombinant human IL-21 protein
Daim duab 5: Recombinant human IL-21 protein txhawb kev tso tawm ntawm IFN-γ los ntawm NK-92
2. NK cell culture kit
Hloov pauv hauv NK tag nrho cov hlwb nthuav dav
Kev hloov pauv hauv NK cell viability
NK cell expansion ratio
Hais txog T&L
T&L Biotechnology Ltd., nrhiav tau nyob rau hauv 2011, tsom rau kev tshawb fawb thiab kev loj hlob ntawm upstream GMP qib raw cov ntaub ntawv thiab reagents ntawm cell thiab noob therapy (CGT). Peb cog lus los muab cov khoom lag luam txhim khu kev qha thiab cov kev pabcuam rau kev ua neej nyob