What is NK-cell therapy?
Har kuni odamda trillionlab hujayralar ko'payadi. Kanserogenlar (chekish, ionlashtiruvchi nurlanish, Helicobacter pylori va boshqalar) ta'sirida har kuni replikatsiya jarayonida 500,000 1 dan XNUMX milliongacha hujayra mutatsiyaga uchrashi mumkin. Ba'zi mutant hujayralar keyinchalik saraton hujayralariga aylanadi.
Immunitetli legion
After thousands of years of evolution, the human body has formed a sophisticated defense system, established a powerful immune corps, and stocked a large number of elite soldiers, always protecting us and keeping us away from cancer. Among them, the bone marrow is the headquarters of the immune system. Here, hematopoietic stem cells differentiate into immune fighters with different functions. They have their own army territory and job responsibilities.
Uchta asosiy armiya mavjud:
1. Asosiy legion: limfotsit
T limfotsitlar Timusga bog'liq limfotsitlar, qon va resirkulyatsiyadagi asosiy limfotsitlar.
B limfotsitlari bursa yoki uning izoaktiv organlarida (suyak iligi) rivojlanadi, ular antigen tomonidan rag'batlantirilgandan keyin antikor ishlab chiqaruvchi plazma hujayralariga ajralib chiqishi mumkin.
NK hujayralari, LAK hujayralari antigen sezgirligining o'ldiruvchi ta'siriga muhtoj emas
2. Yordamchi legion: Antigen taqdimoti
Mononukleer-makrofagli fagotsitoz, hozirgi TD antigeni, immunitetni, o'smaga qarshi ta'sirni, bioaktiv muhit sekretsiyasini boshlaydi.
Doimiy hujayralar antigenni namoyish qilish funktsiyasiga ega bo'lgan heterojen hujayralar guruhidir va sodda T hujayralarini faollashtira oladigan yagona antigen taqdim etuvchi hujayralardir.
3. Boshqa immunitet hujayralari legionlari
Neytrofillar, eozinofil / asosiy granulotsitlar va mast hujayralari, trombotsitlar, qizil qon tanachalari.
NK Cell nima?
Immunitet rölesi jangi: birinchi tayoq-NK xujayrasi
Bizning tanamizdagi immunitet jangi filmda chiqarilgan dushmanga qarshi urush bilan bir xil. Estafeta poygasi singari, bu uchta armiyaning aniq mehnat taqsimotini, puxta jangovar rejasini va dushmanni bir zumda yo'q qilish bo'yicha muvofiqlashtirilgan operatsiyalarni talab qiladi.
qarshi kurashda saraton hujayralari, natural killer (NK) cells bear the brunt. It is the first to directly kill cancer cells when they reach the shish micro environment while secreting secret weapon chemokines to recruit dendritic cells (CD103 + DC). Then, activated dendritic cells carry tumor antigens to the lymph nodes, presenting the characteristics of cancer cells to killer T cells. T cells then rush to the battlefield to kill cancer cells together with NK cells.
Eng kuchli o'ldirish effektiga ega bo'lgan NK hujayrasi
NK hujayralari
To'liq ismi: Natural Killer Cell
Manba: To'g'ridan-to'g'ri suyak iligidan olingan bo'lib, uning rivojlanishi suyak iligi mikro muhitiga bog'liq
Funktsiyasi: NK hujayralari tomonidan o'ldirilgan maqsadli hujayralar asosan o'simta hujayralari, virus bilan zararlangan hujayralar, kattaroq patogenlar (qo'ziqorinlar va parazitlar kabi), allotransplantatsiya qilingan organlar va to'qimalardir.
NK hujayralarining to'liq nomi tabiiy qotil hujayra (NK) bo'lib, u yadro hujayralari legionidagi T va B hujayralari bilan parallel ravishda limfotsitlarning uchinchi guruhidir. NK hujayralari yirik va sitoplazmatik zarrachalarni o'z ichiga oladi, shuning uchun ular yirik zarrachali limfotsitlar deb ataladi. U uchta eng katta xususiyatga ega:
Birinchidan, bu inson tanasining tug'ma immunitet tizimi. Bu, albatta, oldingi safdagi askar. Deyarli barcha o'sma hujayralari birinchi navbatda NK hujayralari tomonidan hujumga uchraydi.
Ikkinchidan, u keng spektrli antitümör ta'siriga ega, o'smaning o'ziga xos tan olinishini talab qilmaydi va hujayra yuzasida asosiy histokompatibilite kompleksi (MHC) inhibitör faolligi bilan cheklanmaydi. Ishga tushirish vaqti eng tezdir va T hujayralari "dushman va dushman" ni ajratib olishdan oldin antigenlar bilan ta'minlanishi kerak.
Uchinchidan, vaziyat haqidagi mulohazalar o'z vaqtida. "Dushman holati" topilgandan so'ng, tezda "xabar beriladi" va butun immun tizimining immunitetni himoya qilish va immunitetni o'ldirish funktsiyalari faollashadi.
Shuning uchun saratonni o'ldiradigan ta'sir kuchli.
Shu bilan birga, inson tanasida NK hujayralarining soni nisbatan kam bo'lib, ular periferik qondagi limfotsitlarning umumiy sonining taxminan 15% ni, taloqda esa taxminan 3-4% ni tashkil qiladi. Ular o'pka, jigar va ichak shilliq qavatida ham paydo bo'lishi mumkin, ammo timus, limfa tugunlari va ko'krak kateterida kam uchraydi.
NK hujayralari saraton hujayralarini qanday o'ldiradi?
NK hujayralari saraton kasalligidan himoya qilishda birinchi o'rinda turadi. NK hujayralari saratonga qarshi uchta ta'sirga ega:
One is the direct killing of tumor cells, killing tumor cells by releasing perforin and granzyme or death receptors; the second is that it acts as a regulatory cell of the immune system by activating cytokines and chemokines, activating T cells, etc. The lethal effect.
The third is the formation of ADCC (antibody-dependent cell-mediated cytotoxicity). When B cells find cancer cells, they will quietly leave specific IgG antibodies on the cancer cells as a mark to remind NK cells to see this mark. NK cells see each other and kill them. With the help of macrophages and B cells, the morale of cancer-killing increased greatly.
NK hujayralari saraton hujayralarini yo'q qiladi
NK hujayralari inson qonida mavjud bo'lib, "birinchi javob beruvchi" hisoblanadi. Bu xuddi tanada navbatchilik qilgan politsiyachiga o'xshaydi. Qon atrofida aylanayotganda, NK hujayralari patrul paytida boshqa hujayralar bilan aloqa qilishni davom ettiradi. Tanadagi hujayralardagi anormallik aniqlanganda, darhol barqaror, aniq, shafqatsizlarcha vaqtni kuting. Ular T hujayralari joylashtirilishidan oldin maqsadli hujayra membranasida perforin va granzimni o'z ichiga olgan sitotoksik zarralarga hujum qilib, ularni chiqaradilar va saraton hujayralarining o'z-o'zini yo'q qilishiga olib keladi. Shuningdek, ular tanada aylanib yuradigan saraton xujayralarini yo'q qilishi va metastazning oldini olishga yordam beradi.
NK hujayralariga asoslangan immunoterapiya
Ular o'simta hujayralarini tezda himoya qilishlari va ularga to'g'ridan-to'g'ri hujum qilishlari mumkin bo'lsa-da, NK hujayralari immunitet tizimining kichik bir qismidir, bu oq qon hujayralarining atigi 10 foizini tashkil qiladi. Va tadqiqot shuni ko'rsatdiki, 25 yoshdan keyin inson immuniteti pasayadi va NK hujayralari soni kamayadi. O'simta bilan og'rigan bemorlarda va o'simta operatsiyasidan keyingi bemorlarda NK hujayralarining soni va faolligi ma'lum darajada o'zgardi va ular antikanser ta'sirini samarali bajara olmaydilar.
Tadqiqotchilar hozirda "asrab olingan" NK hujayra terapiyasiga e'tibor qaratmoqdalar - yaqin qarindosh donorlardan NK hujayralarini to'plash va ularni bemorlarga in'ektsiya qilish. Bu xavfsiz ekanligi isbotlangan va T-hujayrali terapiyadan farqli o'laroq, NK hujayralari qabul qiluvchi to'qimalarda greftga qarshi xost kasalligini keltirib chiqarmaydi.
O'simta uchun NK hujayralarining hozirgi xalqaro strategiyasi immunoterapiya bo'ladi:
1. In vitro faollashtirilgan autolog yoki allogenik NK hujayra terapiyasi;
2. Antikorga xos sitotoksiklikni qo'zg'atish uchun NK hujayralari va monoklonal antikorlarni (masalan, immun nazorat nuqtasi inhibitörleri) birlashtiring;
3. CAR-NK hujayra immunoterapiyasini tuzing.
NK hujayra avto retseptorlarini faollashtiring: NK hujayra membranalarida inhibitor retseptorlarini antitelalar bilan to'sib qo'ying yoki aktivani rag'batlantiring
NK hujayralarining liziz faolligini oshirish uchun retseptorlarni tinglash
Immun tekshiruvi inhibitörleri bilan birgalikda: nazorat nuqtasi terapiyasi, boshqa NK tomonidan boshqariladigan immunoterapiya bilan bir qatorda, hozirgi paytda mavjud bo'lgan davolash usullariga javob bermaydigan ko'plab turdagi o'smalarni yo'naltirishi mumkin.
Kimerik antigen retseptorlari tomonidan o'zgartirilgan NK hujayralari: NK hujayralari samaradorligining o'ziga xosligini sezilarli darajada yaxshilashi mumkin. Bu g'oya CAR-T konstruktsiyasiga o'xshaydi: CAR o'simtaga xos antijenlarni tanib olish uchun hujayradan tashqari tanib olish domenlarini (masalan, scFv) o'z ichiga oladi; transmembran domen va hujayra ichidagi signalizatsiya domeni (CD3z zanjiri) NK hujayralarining faollashishiga olib kelishi mumkin.
NK hujayrasi va T hujayralari terapiyasining farqi nimada?
Saratonga qarshi immunoterapiya sohasida odamlar o'smalarga qarshi T hujayralarini safarbar qilishga e'tibor qaratmoqdalar. Hozirgi vaqtda FDA ikkita CAR-T hujayra terapiyasini ma'qullagan.
Ham T hujayralari, ham NK hujayralari saraton hujayralarini tanib o'ldirishi mumkin, ammo ular har xil yo'llar bilan harakat qilishadi.
T hujayralari o'zlarining maqsad hujayralarining ayrim qismlarini boshqa immun hujayralarga "taqdim etishi" kerak, ularni begona hujayralar deb bilish va T hujayralarini hujum shakllariga birlashtirish.
NK cells recognize the pattern of cancer cell changes and are the first line of defense of the immune system. Unlike T cells, they directly detect and destroy infected and malignant cells without having to be activated or “trained” to respond to cancer cells. However, it is now well known that exposure to cytokines, which are components of the immune system, activates NK cells more effectively.
Tabiiy qotil hujayralar sichqonchaning yashil hujumida ko'rsatilgan. NK hujayralari saraton immunoterapiyasining kaliti bo'lishi mumkin. Moviy rang qon tomirlarini ko'rsatadi. Rasm manbai: doktor Mishel Ardolino va doktor Brayan Vayt
NK hujayra terapiyasining afzalliklari
1. Immun hujayra terapiyasi jarrohlik, kimyoterapiya va radioterapiyadan keyingi to'rtinchi davolash usuli hisoblanadi. NK hujayralari terapiyasi radioterapiya va kimyoterapiya bilan birgalikda jarrohlik yo'li bilan butunlay olib tashlanishi mumkin bo'lmagan o'simta hujayralarini samarali ravishda olib tashlashi mumkin;
2. NK hujayra terapiyasi radiokimyoterapiya bilan birgalikda radiokimyoterapiya samaradorligini oshirishi va yon ta'sirini kamaytirishi mumkin;
3. For advanced cancer patients who are not suitable for surgery, radiotherapy, or chemotherapy, NK cell therapy is a better choice;
4. Jarrohlikdan so'ng NK hujayralari bilan muntazam davolanish saraton kasalligining qaytalanishi va metastazining oldini olish mumkin;
5. Saraton og'rig'ini yo'qotish, uyquni yaxshilash, bemorning hayot sifatini yaxshilash va bemorning hayot tsiklini uzaytirish;
6. Sub-sog'lom odamlar uchun NK hujayra terapiyasidan foydalanish saraton xavfini kamaytirishi mumkin.
NK Cell Therapy xalqaro yangilanishi
Yaponiyaning NK hujayra immunoterapiyasi
In order to improve the activity and number of NK cells in the body, Japanese scientists have invented a multiplier method, which is to extract 50ml from human blood, isolate a small amount of NK cells and then expand the culture to increase the number to the original 1000 times, the number reaches 1 billion to 5 billion and is then returned to the body, a large number of NK cells will circulate 3000 to 4000 times with the blood system, killing cancer cells, aging cells, diseased cells, bacteria and viruses in the body Once again, to achieve the purpose of anti-cancer, improve immunity and prolong survival.
Amerikalik NK hujayra immunoterapiyasi
Qo'shma Shtatlar NK hujayralarini saratonga qarshi immunoterapiya sinovlariga kiritdi!
bilan ayol o'tkir miyeloid leykemiya (AML) is dying after repeated chemotherapy failures. As a final attempt, she received an experimental cell infusion of natural killer (NK) cells donated by her son. After 4 days, the osmotic skin lesions disappeared, and soon she entered a state of relief.
NK hujayra terapiyasi hali ham Qo'shma Shtatlarda faqat erta klinik sinovlarda bo'lsa-da, klinik tadqiqotlar ortib bormoqda.
A clinical trial led by Washington University in St. Louis showed that approximately 12 patients with AML and miyelodisplastik sindrom (MDS) received NK cells. Half of the patients entered the remission period.
At present, MD Anderson at Dana Faber Cancer Institute is conducting a clinical trial, which will test the efficacy of NK cell therapy in patients with hematological tumors that relapse after stem cell transplantation. Patients who want to know the details can call + 91 96 1588 1588.
NK hujayra terapiyasiga kim mos keladi?
1. Shish jarrohligigacha jismoniy holati yomon, operatsiyadan keyin sekin tiklanish va yashirin saraton hujayralari to'liq yo'q qilinishidan qo'rqish.
2. After radiotherapy and chemotherapy, the immune system is low, the side effects are obvious (such as loss of appetite, nausea, hair loss, skin inflammation, etc.), and patients expect to increase the effect of chemoradiation.
3. Terapevtik ta'sirga erishish uchun turli xil davolash usullaridan foydalanishni istagan bemorlar radioterapiya va kimyoviy terapiyaning yon ta'siridan qo'rqishadi.
4. Rivojlangan saraton hujayralari bo'lgan bemorlar butun vujudga tarqalib ketishdi, ammo an'anaviy davolash usullari kuchsiz bo'lib qoldi va umr ko'rish muddatini uzaytiradigan va hayot sifatini yaxshilaydigan bemorlar.
NK hujayra terapiyasining davolash jarayoni
1. Blood collection: Extract 30–50 ml of peripheral blood of cancer patients and extract mononuclear cells;
2. Laboratory culture: In the laboratory, conduct NK cell induction and expansion for a period of 5-7 days;
3. Return: After the NK cell culture is completed, it is returned to the cancer patient like an infusion.
NK hujayra terapiyasining davosi
Case Manba: Yaponiyadagi nufuzli NK hujayrali terapiya klinikasi
Ms. Zheng, 50, was diagnosed with advanced pankreatik saraton (pancreatic tail), transferred to the liver, lungs, and pleura, and was diagnosed with cancerous peritonitis (chest wall, multiple nodules in the lungs). . After one cycle of Gemcitabine Gatige, the effect was not satisfactory, CA19-9 rose from 257,531 to 318,417. On the advice of the doctor, the whole genome was sequenced, and the result did not have any meaningful mutations. The doctor said that she had three months to six months at most. According to expert recommendations, Ms. Zheng began to reinject highly activated NK cells at a frequency of once every two weeks.
Immediately after finishing the first return, Ms. Zheng’s most obvious feeling was that she felt full of energy. She was always weak, and the pain symptoms were alleviated. With appetite, you can eat some light food.
Kutilmagan tarzda davolanish juda silliq kechdi. Birinchi muolajadan so'ng CA19-9 to'g'ridan-to'g'ri 7355 ga tushirildi. To'rtinchi darajali yuqori faollashtirilgan NK hujayralarini davolashdan so'ng u 141 ga tushdi.
2016 yil oxirida qayta tekshirilgan KT tasvirlari jigar va o'pka bronxial limfa tugunlari kabi metastatik lezyonlar yo'qolganligini ko'rsatdi. Birlamchi joydagi oshqozon osti bezi saratoni ham yarmidan ko'proq kamaydi.
To'liq tiklanmagan bo'lsa-da, davolanish jarayoni juda yumshoq. Davolashni boshlashdan oldin, eng yomon tayyorgarlik ko'rilgan va hatto davolanish kursi davom eta olmasligi mumkin, ammo birinchi davolanish kursining oxirida bemorning jismoniy holati ancha yaxshilandi.
