Kev Tshawb Fawb Ntawm Tes: Tsim lub cim tshiab ntawm kev ua haujlwm tau zoo, tsis muaj tshuaj lom tsawg-qog nqaij hlav-txwv IL-15 cov tshuaj

Kev Tshawb Fawb Xov Xwm luam tawm online cov ntawv tshawb fawb Tumor-conditional IL-15 pro-cytokine rov ua haujlwm tiv thaiv qog tiv thaiv kab mob nrog txwv tsis pub muaj tshuaj lom, uas tau ua tiav los ntawm Peng Hua, tus kws tshawb fawb ntawm lub koom haum ntawm Biophysics, Suav Academy ntawm Kev Tshawb Fawb, thiab Fu Yangxin, xibfwb ntawm University of Texas Southwestern Medical Center. Kev tshawb fawb thiab kev txhim kho ntawm ib tiam neeg tshiab ntawm kev ua haujlwm tau zoo, tsis muaj tshuaj lom tsawg-qog nqaij hlav-txwv IL-15 cov tshuaj.

Tam sim no, feem ntau cov tshuaj tiv thaiv kab mob qog noj ntshav tsom mus rau thaiv cov kab mob tiv thaiv kab mob lossis ua kom muaj cov cim qhia tiv thaiv kab mob. Txawm li cas los xij, kev kho mob hnyav ntsig txog kev muaj tshuaj lom thiab cov qog nqaij hlav tsis zoo tshwm sim los ntawm cov qog nqaij hlav tsis zoo tsom mus rau qhov txwv tsis pub siv tshuaj kho mob. IL-2 yog pleiotropic cytokine uas tuaj yeem nthuav T cells thiab NK cells. IL-2 kuj tseem tuaj yeem ua kom cov tshuaj tiv thaiv kab mob T cells (Kev tswj hwm T cells, Treg), ua rau muaj kev cuam tshuam T cell tuag (Ua kom muaj kev tuag ntawm tes, AICD), txhawb cov hlab ntshav endothelial, thiab ua rau muaj kev phiv loj, yog li nws tsis tau siv rau hauv tsev kho mob. Piv nrog IL-2, IL-15 muaj cov txiaj ntsig zoo hauv qab no hauv kev kho qog: IL-15 tuaj yeem zam kev ua kom tuag ntawm tes thiab ua rau cov khoom lag luam thiab ua kom lub xeev ruaj khov ntawm kev nyob ntev T hlwb; IL-15 yuav tsis nthuav ntxiv Treg cells; IL-15 tsis ua rau vascular endothelial cells ua rau muaj kev phiv tshwm sim. Yog li, tam sim no IL-15 yog qhov muaj peev xwm tiv thaiv qog nqaij hlav qog noj ntshav cytokine. Txawm li cas los xij, IL-15 cov neeg txais khoom tau nthuav dav nthuav tawm hauv cov ntaub so ntswg, thiab IL-15 kev txhaj tshuaj tuaj yeem ua rau muaj kev phom sij phom sij thiab txwv txoj kev kho mob ntawm cov qog. Raws li kev tiv thaiv kab mob tiv thaiv kab mob ntawm IL-15, cov kws tshawb fawb tau tsim muaj txiaj ntsig zoo thiab muaj tshuaj lom tsawg los tiv thaiv qog noj ntshav prodrug-pro-IL-15 thawj zaug. Cov kws tshawb fawb tau txuas nrog cov ntawv txuas ntxiv ntawm IL-15Rβ mus rau N-terminus ntawm IL-15 los ntawm txheej txheej polypeptide ntawm cov hlau matrix protease-14 (uas tau hais tawm ntau hauv cov nqaij mos thiab qis hauv cov nqaij ib txwm muaj) rau kev thim rov qab. Txhawm rau thaiv cov haujlwm ntawm IL-15. Pro-IL-15 nyob rau hauv lub xeev kaw ntawm ib puag ncig kom tsis txhob tso tawm cov dej num thiab ua rau muaj tshuaj lom; thaum cov tshuaj nkag mus rau hauv cov qog nqaij hlav, lub siab qhia tawm metalloproteinase-14 hauv cov qog zom zaws thiab tshem tawm qhov sib txuas peptide ntu, tso cov haujlwm ntawm IL-15, thiab ua kom cov tshuaj tiv thaiv qog tiv thaiv qog.

Pro-IL-15 txo cov kev ua kom lub cev muaj kuab lom los ntawm kev thaiv qhov ua kom nthuav dav thiab nthuav dav ntawm ib puag ncig NK cells thiab T cells, tab sis khaws cov peev txheej tiv thaiv qog zoo. Cov tshuaj tiv thaiv qog nqaij hlav ntawm Pro-IL-15 nyob ntawm CD8+ T cells thiab cov txiaj ntsig ua rau lub cev IFN-γ muaj nyob hauv cov qog. Kev kho mob Pro-IL-15 ua rau nce qia cell zoo li TCF1+Tim-3-CD8+ T cells hauv cov nqaij mos, thiab pab kov yeej kev tiv thaiv kab mob tiv thaiv kab mob (ICB). Ib qho ntxiv, hauv" txias" cov qauv qog uas tsis muaj kev tiv thaiv kab mob ntawm tes qis xws li TUBO, pro-IL-15 ua ke nrog tyrosine kinase inhibitor (TKI) tsom kev kho mob ua rau muaj kev sib xyaw ua haujlwm tiv thaiv qog nqaij hlav, qhia tau tias pro-IL-15 Pab kov yeej kev tiv thaiv rau kev kho mob. Qhov kev tshawb fawb no yuav daws qhov teeb meem ntawm cov tshuaj lom loj thiab phiv tshwm sim hauv kev siv tshuaj kho mob ntawm cytokines, thiab muaj cov lus qhia tseem ceeb rau kev kov yeej kev tiv thaiv kab mob tiv thaiv kev tiv thaiv kev ua siab ntev thiab txhim kho kev ua tau zoo ntawm cov tshuaj.