What is NK-cell therapy?
Trillions of cells replicate in a person every day. Under the influence of carcinogens (smoking, ionizing radiation, Helicobacter pylori, etc.), about 500,000 to 1 million cells can mutate during the replication process every day. Some mutant cells further become cancer cells.
Ibutho lomzimba
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.
Kunamabutho amathathu amakhulu:
1. ICore Legion: ILymphocyte
Ama-lymphocyte T Ama-lymphocyte ancike kuma-Thymus, ama-lymphocyte aphambili egazini nasekubuyiseleni emzimbeni
Ama-lymphocyte B akhula ku-bursa ye-bursa noma ezithweni zayo ezingasebenzi (umnkantsha), ongahlukanisa abe ngamaseli e-plasma akhiqiza ama-antibody ngemuva kokuvuselelwa yi-antigen
Amaseli we-NK, amaseli we-LAK awadingi umphumela wokubulala we-antigen sensitization
2. Ibutho Elisizayo: Isethulo se-Antigen
I-mononuclear-macrophage phagocytosis, ekhona i-TD antigen, iqala ukuphendula komzimba, umphumela wokulwa nesimila, uketshezi kwemithombo yezindaba
Amaseli e-DC ayiqembu lamaseli angafani anemisebenzi enamandla kakhulu yokwethula i-antigen futhi yiwona kuphela amangqamuzana e-antigen-ethula ubuchwepheshe angavula amaseli we-T angenalwazi
3. Amanye amabutho amasosha omzimba
Ama-neutrophils, ama-erosinophilic / ama-granulocyte ayisisekelo namaseli ama-mast, ama-platelets, amaseli abomvu egazi.
Yini i-NK Cell?
Impi yokudluliswa komzimba
Impi yokuzivikela emizimbeni yethu ifana ncamashi nempi yokulwa nezitha ekhonjiswe kumuvi. Njengomjaho odlulisanayo, kudinga ukuhlukaniswa okucacile kwemisebenzi yamabutho amathathu, uhlelo lokulwa ngokucophelela, nemisebenzi ehambisanayo yokuqeda isitha ngasikhathi sinye.
Empini yokulwa amangqamuzana omdlavuza, natural killer (NK) cells bear the brunt. It is the first to directly kill cancer cells when they reach the isisu 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.
I-NK Cell enamandla amakhulu okubulala
Amaseli we-NK
Igama eligcwele: Iseli Yombulali Wemvelo
Umthombo: Kususelwa ngqo kumnkantsha wethambo, ukukhula kwawo kuncike kwimvelo encane yomnkantsha
Umsebenzi: Amaseli okuhlosiwe abulawa amaseli e-NK ikakhulukazi amaseli e-tumor, amaseli atheleleke ngegciwane, amagciwane amakhulu (njengesikhunta nama-parasites), izitho ezitshaliwe kanye nezicubu.
Igama eligcwele lamaseli e-NK i-Natural Killer Cell (NK), okuyiqembu lesithathu lama-lymphocyte ngokuhambisana namaseli T kanye no-B ku-core cell legion. Amaseli e-NK makhulu futhi aqukethe izinhlayiya ze-cytoplasmic, ngakho abizwa ngokuthi ama-lymphocyte anezinhlayiyana ezinkulu. Inezici ezintathu ezinkulu:
Okokuqala, amasosha omzimba womuntu azalwa nawo. Impela yisosha elihamba phambili. Cishe wonke amangqamuzana ezimila azohlaselwa ngamaseli we-NK kuqala.
Okwesibili, inomphumela obanzi we-antitumor, ayidingi ukuqashelwa okuqondene nesimila, futhi ayinqunyelwe umsebenzi omkhulu we-histocompatibility complex (MHC) ebusweni beseli. Isikhathi sokuqala yisona esisheshayo, futhi ama-T cell adinga ukwethulwa ngama-antigen ngaphambi kokuthi ahlukanise phakathi "kwesitha nesitha".
Okwesithathu, impendulo yesimo ifike ngesikhathi. Lapho "isimo sesitha" sesitholakele, "kuyabikwa" ngokushesha futhi imisebenzi yokuvikela amasosha omzimba kanye nokubulala amasosha omzimba wohlelo lonke lomzimba.
Ngakho-ke, umphumela wokubulala umdlavuza unamandla.
Kodwa-ke, inani lamaseli e-NK emzimbeni womuntu lincane, libala cishe i-15% yenani eliphelele lama-lymphocyte egazini lomngcele, futhi cishe amaphesenti ama-3 kuya ku-4% ebuchosheni. Zingavela futhi emaphashini, esibindini nasemathunjini, kepha kwi-thymus, i-lymph node ne-Chest catheter akuvamile.
Amangqamuzana e-NK abulala kanjani amangqamuzana omdlavuza?
Amaseli e-NK adlala indima ebalulekile emgqeni wokuqala wokuzivikela kumdlavuza. Amaseli we-NK anemiphumela emithathu elwa nomdlavuza:
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.
Amaseli e-NK aqeda amangqamuzana omdlavuza
Amaseli we-NK akhona egazini lomuntu futhi "angabaphenduli bokuqala". Kufana nephoyisa ebelisemsebenzini emzimbeni. Njengoba igazi ligijima, amangqamuzana e-NK aqhubeka nokuxhumana namanye amaseli ngenkathi ezulazula. Lapho kutholakala okungajwayelekile kumaCell body, ngokushesha kuzinzile, kunembile, kulinde ngesihluku isikhathi sokubhekana nakho. Bahlasela futhi badedele izinhlayiya ze-cytotoxic eziqukethe i-perforin ne-granzyme kulwelwesi lweseli okuqondiswe kulo ngaphambi kokuthi kufakwe amaseli we-T, okudala ukuzilimaza kwamangqamuzana omdlavuza. Bangakwazi futhi ukuqeda amangqamuzana omdlavuza ajikeleza emzimbeni futhi asize ukuvimbela imastastasis.
Ukwelashwa komzimba okwenziwe ngamaseli we-NK
Yize engavikela ngokushesha futhi ahlasele ngqo amaseli ezinwele, amangqamuzana e-NK ayingxenye encane kuphela yesistimu yomzimba, ebala kuphela u-10% wamaseli amhlophe egazi. Futhi ucwaningo luthole ukuthi ngemuva kweminyaka engama-25 ubudala, ukuzivikela komzimba komuntu kuyehla futhi nenani lamaseli e-NK liba lincane. Inombolo nomsebenzi wamaseli e-NK ezigulini ezinezilonda kanye nasezigulini ngemuva kokuhlinzwa kwesimila kushintshile kwaba sezingeni elithile, futhi abakwazi ukuletha umphumela we-anticancer ngempumelelo.
Abaphenyi manje sebegxile ekwelapheni-ukuqoqa amaseli e-NK cell "eqoqa amaseli we-NK avela kubaxhasi abasondelene futhi bawajova ezigulini. Lokhu kufakazelwe ukuthi kuphephile, futhi ngokungafani nokwelashwa kwe-T cell, amaseli we-NK awasibangeli isifo se-graft-versus-host kwizicubu zomamukeli.
Amasu wamanje wamazwe omhlaba wonke we-NK cell for tumor immunotherapy yilezi:
1. In vitro activated autologous or allogeneic NK cell therapy;
2. Combine NK cells and monoclonal antibodies (such as immune checkpoint inhibitors) to induce antibody-specific cytotoxicity;
3. Yakha i-CAR-NK cell immunotherapy.
Yenza kusebenze i-NK cell auto receptors: Vimba ama-receptor inhibitory kuma-NK cell ulwelwesi ane-antibodies, noma uvuselele i-activa
ama-receptors ukukhulisa umsebenzi we-NK cell lysis
Ngokuhlanganiswa nama-immune checkpoint inhibitors: ukwelashwa kokuhlola okuhlanganiswe nenye i-immunotherapy eqondiswa yi-NK kungakhomba izinhlobo eziningi zamathumba ezingaphenduli njengamanje ekwelashweni okukhona.
NK cells modified by chimeric antigen receptor: can significantly improve the specificity of NK cell efficacy. This idea is similar to the construction of CAR-T: CAR includes extracellular recognition domains (such as scFv) to recognize tumor-specific antigens; a transmembrane domain, and an intracellular signaling domain (CD3ζ chain) can induce NK cells activation.
Uyini umehluko phakathi kokwelashwa kwe-NK cell ne-T cell?
Emkhakheni we-immunotherapy yomdlavuza, abantu bebelokhu begxile ekugqugquzeleni amaseli we-anti-tumor T. Njengamanje, i-FDA ivume ukwelashwa okubili kwe-CAR-T.
Womabili amaseli we-T namaseli we-NK angawabona futhi abulale amangqamuzana omdlavuza, kepha aqhubeka ngezindlela ezihluke kakhulu.
Amaseli we-T adinga "ukwethula" ezinye izingxenye zamangqamuzana awo aqondisiwe kwamanye amaseli omzimba ukuze awabone njengamaseli angaphandle futhi ahlanganise amaseli we-T abe amaphethini wokuhlasela.
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.
Amaseli okubulala wemvelo akhonjiswa kumathumba egundane wokuhlaselwa okuluhlaza okotshani. Amaseli e-NK angaba ukhiye womdlavuza we-immunotherapy. Okuluhlaza okwesibhakabhaka kukhombisa imithambo yegazi. Umthombo wesithombe: UDkt Michele Ardolino noDkt Brian Weist
Izinzuzo zokwelashwa kwe-NK cell
1. Ukwelashwa kwamangqamuzana amasosha omzimba kuyindlela yesine yokwelapha ngemva kokuhlinzwa, ukwelapha ngamakhemikhali kanye ne-radiotherapy. I-NK cell therapy ehlanganiswe ne-radiotherapy kanye ne-chemotherapy ingasusa ngokuphumelelayo amangqamuzana e-tumor angakwazi ukususwa ngokuphelele ngokuhlinzwa;
2. Ukwelashwa kwamaseli e-NK okuhlanganiswe ne-radiochemotherapy kungathuthukisa ukusebenza kwe-radiochemotherapy futhi kunciphise imiphumela emibi;
3. For advanced cancer patients who are not suitable for surgery, radiotherapy, or chemotherapy, NK cell therapy is a better choice;
4. Ukwelashwa njalo ngamaseli we-NK ngemuva kokuhlinzwa kungavimbela ukuphindaphinda kanye ne-metastasis yomdlavuza;
5. Ukudambisa izinhlungu zomdlavuza, ukuthuthukisa ukulala, ukuthuthukisa ikhwalithi yempilo yesiguli, nokwandisa umjikelezo wokuphila wesiguli;
6. Kubantu abanempilo encane, ukusetshenziswa kwe-NK cell therapy kunganciphisa ingozi yomdlavuza.
Ukuvuselelwa Komhlaba Wonke kwe-NK Cell Therapy
I-Japanese NK cell immunotherapy
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.
I-American NK cell immunotherapy
I-United States ifake amaseli e-NK ekuhlolweni kwe-cancer immunotherapy!
A woman with i-acute myeloid leukemia (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.
Although NK cell therapy is still only in early clinical trials in the United States, clinical research is increasing.
A clinical trial led by Washington University in St. Louis showed that approximately 12 patients with AML and i-myelodysplastic syndrome (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.
Ngubani ofanele ukwelashwa kwe-NK cell?
1. Iziguli ezinomzimba omubi ngaphambi kokuhlinzwa kwesimila, ukululama kancane ngemuva kokuhlinzwa, nokwesaba ukuthi amangqamuzana omdlavuza wemilingo angaqedwa ngokuphelele.
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. Iziguli ezifisa ukusebenzisa izindlela ezahlukahlukene zokwelapha ukufeza imiphumela yokwelashwa ngenxa yokwesaba imiphumela emibi ye-radiotherapy kanye ne-chemotherapy.
4. Iziguli ezinamaseli omdlavuza asethuthukile zisabalale kuwo wonke umzimba, kepha izindlela zokwelashwa ezivamile bezingenamandla, neziguli ezilindele ukwelula isikhathi sokuphila nokwenza ngcono impilo.
Inqubo yokwelashwa kwe-NK cell therapy
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.
Icala lokwelashwa lokwelashwa kwe-NK cell
Case Source: An authoritative NK cell therapy clinic in Japan
Ms. Zheng, 50, was diagnosed with advanced umdlavuza pancreatic (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.
Kungalindelekile, impatho ibibushelelezi impela. Ngemuva kokwelashwa kokuqala, i-CA19-9 yehliswa ngqo yaba ngu-7355. Ngemuva kokwelashwa kwesine okusebenze kakhulu kwe-NK cell, yehle yaya ku-141.
At the end of 2016, the rechecked CT images showed that metastatic lesions such as liver and lung bronchial lymph nodes had disappeared. Pancreatic cancer at the primary site has also shrunk by more than half.
Yize ingakatholakali ngokuphelele, inqubo yokwelashwa ibushelelezi kakhulu. Ngaphambi kokuqala ukwelashwa, kwenziwe amalungiselelo amabi kakhulu, futhi ngisho nenkambo yokwelashwa kungenzeka ingakwazi ukuqhubeka, kepha lapho kuphele inkambo yokuqala yokwelashwa, isimo somzimba sesiguli sesithuthuke kakhulu.
