ROR1 tsom monoclonal tshuaj tiv thaiv cirmtuzumab + BTK inhibitor Imbruvica ua tiav kev tshem tawm tus nqi ntawm 50%, kev kho mob tau txais txiaj ntsig 100%

Kev Kho Mob Lub Pob Ntseg yog lub chaw kho mob-qib biopharmaceutical lub tuam txhab tau mob siab rau kev tsim cov qog tshuaj tshiab rau kev kho mob qog nqaij hlav nrog mob loj tsis tau xav tau. Kev tsom xam ntawm nws txoj kev txhim kho tshuaj yog nyob rau kev cog lus tab sis piav tsis tau hais txog kab mob khees-xaws hais txog kev mob caj dab. Tsis ntev los no, lub tuam txhab tshaj tawm cov ntaub ntawv tshiab kawg ntawm cirtuzumab ua ke nrog Imbruvica (ibrutinib) hauv kev kho mob lossis rov ua haujlwm mantle cell lymphoma (R / R MCL) theem I / II CIRLL kev kawm (txij li lub Peb Hlis 6, 2020)

cirmtuzumab yog ib qho monoclonal antibody uas tsom lub npe tshuaj tiv thaiv (receptor) tyrosine kinase-zoo li tus ntsuag ntsuag receptor 1 (ROR1) txoj hauv kev. Imbruvica yog thawj-hauv-chav kawm qhov ncauj Bruton tyrosine kinase (BTK) inhibitor, uas tau sib koom tsim thiab ua lag luam los ntawm AbbVie' s Pharmacyclics thiab Johnson& Johnson' s Janssen Biotechnology.

Cov neeg mob R / R MCL nkag rau hauv CIRLL txoj kev tshawb nrhiav yav dhau los tau txais ntau yam kev kho mob (nruab nrab: 2), suav nrog kev kho mob, kev kho mob qog nqaij hlav hauv hlwb (SCT), autologous SCT thiab CAR-T txoj kev kho, autologous SCT thiab allogeneic SCT, Imbruvica thiab rituximab Cov.

Cov txiaj ntsig tau pom tias nrog kev soj ntsuam nruab nrab ntawm 6.4 lub hlis, ntawm 12 tus neeg mob evaluable, qhov kev teb tag nrho (CR) yog 50% (6/12) thiab ib feem ntawm tus lej teb (PR) yog 33% (4/12) ), tus kab mob tswj kom lub cev tsis khov (SD) yog 17% (2/12), cov lus teb tau zoo tshaj plaws (ORR=CR + PR) yog 83%, tus nqi kho mob (CR + PR {{16 }} SD) yog 100%.

Ib qho ntawm 6 CR tus neeg mob tau lees paub tias yog ua tiav kev kho mob metabolic (CMR) los ntawm CT scan, thiab pob txha caj qaum ua kom tiav. Txhua tus neeg 6 CR tus neeg mob txuas ntxiv tau txais kev zam kom tiav, thiab 1 tus neeg mob tau txais kev kho kom tiav tag nrho rau ntau dua 21 lub hlis. Nws tsim nyog teev tias 4 ntawm 6 CR tus neeg mob ua tiav kev zam tiav tsis pub dhau 4 lub hlis txij li tau txais kev kho mob cirmtuzumab thiab Imbruvica ua ke. Hauv txoj kev tshawb fawb no, kev sib xyaw ntawm cirmtuzumab thiab Imbruvica tau pom zoo zoo, thiab qhov tsis zoo tshwm sim tau ua raws li Imbruvica monotherapy. Tsis muaj koob tshuaj-limiting toxicity, tsis tshem tawm, tsis muaj qhov tshwm sim tsis zoo tshwm sim los ntawm cirmtuzumab.

Hun Ju Lee, MD, tus kws tshawb nrhiav txog CIRLL chav kuaj mob thiab koom nrog tus xibfwb ntawm lymphoma thiab myeloma ntawm University of Texas MD Anderson Cancer Center, hais tias:" Cirmtuzumab thiab Imbruvica ua ke kev kho mob ntawm cov neeg mob nrog R / R MCL tau ua tiav tus nqi siab ntawm kev ua tiav kev kho kom tiav, Tus nqi kho mob tag nrho yog siab dua yav dhau los tshaj tawm Imbruvica monotherapy. Cov ntaub ntawv no tau txhawb nqa, tshwj xeeb xav tias qee cov neeg mob no yav tas los tau txais ntau yam kev kho mob. Cov neeg mob MCL hauv kev tsim dua tshiab tseem yuav tsum tau ua siab ntev thev dhau txoj kev kho kev sib deev kom muab tau kev kho mob tob tob thiab ntev dua."

cirmtuzumab mechanism ntawm kev ua-thaiv WNT5A txoj hauv kev, tiv thaiv kev mob qog nqaij hlav cancer thiab metastasis

cirmtuzumab yog ib qho tshuaj monoclonal antibody uas yog lub hom phiaj ROR1, uas yog lub hom phiaj tseem ceeb rau kev kho mob qog. Qhov no yog cov carcinoembryonic antigen uas tsis tau hais tawm tsis zoo rau cov neeg laus lub hlwb, thaum ua haujlwm thiab hais tawm ntawm cov qog nqaij hlav, Yuav muab cov qog ciaj thiab kev ua kom zoo dua.

Cov kws tshawb nrhiav ntawm University of California San Diego Cov Tsev Kawm Ntawv Tshuaj Kho Mob pom tau tias kev hais txog lub hlwb tseem ceeb ntawm ROR1 yog tus yuam sij tshwj xeeb rau ROR1 qhia cov qog. Cirmtuzumab tau tsim raws li kev pom ntawm no. Lub cev tiv thaiv kab mob tuaj yeem khi rau tus qauv tseem ceeb ntawm ROR1, uas yog qhia tau zoo nyob rau hauv ntau cov qog nqaij hlav txawv tab sis tsis qhia nyob rau hauv cov ntaub so ntswg ib txwm muaj. Cov kev tshawb fawb qhia tau pom tias thaum cirmtuzumab ua ke nrog ROR1, nws tuaj yeem thaiv WNT5A kev taw qhia, inhibit qog cell proliferation, tsiv teb tsaws thiab muaj sia nyob, thiab ntxias cov nqaij hlav sib txawv.

Tam sim no, cirmtuzumab nyob hauv kev txhim kho hauv chaw kho mob. Cirmtuzumab thiab Imbruvica hauv kev kho mob ntawm MCL thiab mob qog nqaij hlav ntshav siab (CLL) yog nyob rau theem I / II cov chaw kuaj mob. Txuas ntxiv, cirmtuzumab ua ke nrog paclitaxel tab tom kho theem I kev soj ntsuam kuaj mob rau kev kho mob cancer mis mob ntau yam.