Sakamako suna nuna cewa mesothelin-niyya TIKE na iya aiki tare da daidaitattun kulawa na yanzu kuma yana ba da fa'ida koda a cikin yanayin hypoxic na ƙwayar cuta mai ƙarfi.
GT Biopharma, Inc., wani kamfani na immuno-oncology na asibiti wanda ya mayar da hankali kan haɓaka sabbin hanyoyin kwantar da hankali dangane da keɓaɓɓiyar keɓaɓɓiyar kisa ta Kamfani (NK), dandamalin fasaha na furotin na TriKE®, ya gabatar da cikakkun bayanai waɗanda ke nuna sabon littafinsa na TriKE tuki NK. Immunotherapy cell akan ciwon huhu mara ƙananan ƙwayar cuta (NSCLC) a cikin ƙananan ƙwayar cuta mai ƙarfi a cikin ESMO's Targeted Anticancer Therapies Congress (TAT).
Gregory Berk, MD, Shugaban Kamfanin R&D da Babban Jami'in Kula da Lafiya ya lura, "Wannan shaidar farko ta asibiti ta nuna, duk da bambancin rarraba ƙwayoyin rigakafi na marasa lafiya na Stage IVB NSCLC, mesothelin-niyya TIKE na iya aiki tare da daidaitattun kulawa na yanzu kuma ba da fa'ida har ma a cikin yanayin hypoxic na ƙaƙƙarfan ƙwayar cuta, wanda ya cancanci ƙarin bincike na wannan labari, wanda aka yi niyya na TIKE.
Tuki NK cell immunotherapy a kan NSCLC, a cikin mahallin hypoxia, ta amfani da Tri-Specific Killer Engager (TriKE®)
Bayan Fage - A halin yanzu, ana gwada masu yin kisa na musamman (TriKE®) a cikin asibiti don magance cutar sankarar bargo da lymphoma. Wadannan CD16/FcγRIII na TriKE's giciye da kuma antigen tumor akan kwayoyin NK wanda ke tafiyar da cytotoxicity yayin da IL15 ke ba da sigina na rayuwa da yaduwa zuwa kwayoyin NK. Mesothelin (MSLN), a halin yanzu shine antigen tumor da aka yi niyya a cikin cututtuka daban-daban ciki har da NSCLC. Binciken na yanzu wanda dakin gwaje-gwaje na Dokta Jeff Miller ya gudanar, Jami'ar Minnesota, ya kimanta ko MSLN-wanda aka yi niyya TIKE zai iya fitar da cytotoxicity zuwa kwayoyin NSCLC a duk matakan cututtuka a gaban hypoxia, kalubale a cikin ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta ta NSCLC.
Tsarin nazari da bincike - Yin amfani da ƙwayoyin jini guda ɗaya (PBMC) da aka tattara daga marasa lafiya na NSCLC, (1) kafin marasa lafiya su fara jiyya na yau da kullum, (2) bayan jiyya na farko da (3) a ci gaba da cututtuka inda ya dace. Binciken ya kalubalanci PBMC mai haƙuri tare da layin salula na NSCLC (NCI-H460) don 5 hours a gaban monensin da brefeldin A, aunawa degenranulation (CD107a) da kuma samar da cytokine (IFNγ) ta hanyar cytometry mai gudana (rayuwa, CD56 + / CD3-sel). ). Idan aka kwatanta da ƙwayoyin NK kadai (NT); Kwayoyin NK kadai tare da miyagun ƙwayoyi ('TriKE'); ko Kwayoyin NK tare da ƙari kadai.
results
NSLC sun canza sel NK - Bambance-bambancen yawa na ƙididdigar ƙwayoyin rigakafi a matakin farko ko ƙarshen matakin ƙungiyoyin haƙuri an yi su ta amfani da software na Astrolabe Diagnostics. TriKE ya sami damar haifar da ayyuka masu mahimmanci (p <0.0001) akan ƙwayoyin H460 don ƙungiyoyin biyu. Binciken ya nuna yawan adadin CD56+/CD16+ NK da ƙananan CD33+/CD14-myeloid sel a farkon marasa lafiya idan aka kwatanta da marasa lafiya marasa lafiya kafin fara jiyya. Rashin CD16, wanda ke tafiyar da cytotoxicity, da kuma yawan ƙwayoyin myeloid, wanda zai iya hana aikin NK cell, da shawarar marasa lafiya na NSCLC na ƙarshen zamani na iya amsawa daban-daban ga ilimin halitta wanda ke nufin NK cell cytotoxicity.
Mesothelin-niyya TIKE yana tafiyar da aikin kwayar NK ba tare da la'akari da matakin cuta ba kuma a duk matakan jiyya: Yayin da hypoxia ke lalata cytotoxicity na NK cell, MSLN-wanda aka yi niyya TriKE na binciken ya inganta NK cell cytotoxicity na kwayoyin cutar ciwon huhu (H460) bayan bayyanar hypoxia na tsawon kwanaki 7. , a lokacin bayyanar da hypoxia da kuma a cikin binciken kanta. Bayanan sun nuna cewa TriKE ya haifar da lalata da kuma samar da cytokine a cikin kwayoyin NK masu haƙuri a lokacin da ke cikin ƙwayoyin tumor (H460) a duk matakan jiyya (kafin jiyya, bayan jiyya na farko da kuma ci gaba).
Kammalawa - Wannan shaida na farko na asibiti ya nuna, duk da bambanci a cikin rarraba kwayoyin rigakafi na Stage IVB NSCLC marasa lafiya, mesothelin-niyya TIKE na iya aiki tare da tsarin kulawa na yanzu kuma ya ba da fa'ida har ma a cikin yanayin hypoxic na ƙwayar cuta mai ƙarfi.
ABUBUWAN DA ZA KU GUDU DAGA WANNAN LABARI:
- , the Company’s President of R&D and Chief Medical Officer noted, “This pre-clinical evidence suggests, despite the difference in circulating immune cells of Stage IVB NSCLC patients, a mesothelin-targeted TriKE can work alongside current standard of care and provide benefit even in the hypoxic environment of a solid tumor, meriting further investigation of this novel, targeted TriKE.
- Jeff Miller’s laboratory, University of Minnesota, evaluated whether a MSLN-targeted TriKE could drive cytotoxicity towards NSCLC cells at all stages of disease in the presence of hypoxia, a challenge in the NSCLC tumor microenvironment.
- The data demonstrated that TriKE induced degranulation and cytokine production in patient NK cells when in the presence of tumor cells (H460) at all stages of treatment (before treatment, after initial treatment and at progression).
