Menene CAR T-Cell magani?
CAR T-Cell far, wanda cikakken sunansa Chimeric Antigen Receptor T-Cell Immunotherapy,. Wannan sabon nau'in maganin tantanin halitta ne wanda aka yi amfani dashi shekaru da yawa, amma an inganta shi kawai kuma an yi amfani dashi a asibiti a cikin 'yan shekarun nan. Hakazalika da sauran immunotherapy, ainihin ka'idarsa ita ce amfani da ƙwayoyin rigakafi na majiyyaci don share ƙwayoyin cutar kansa, amma bambancin shine cewa wannan maganin tantanin halitta ne, ba magani ba.
Tsarin aikin C-T-Cell
1: Kebe garkuwar jikin T daga masu cutar kansa.
2: Using genetic engineering technology to add a chimeric antibody that recognizes tumo cells and activates T cells to kill tumor cells at the same time, T cells instantly turn into tall CAR-T cells. It is no longer an ordinary T cell, it is a “terrorist” T cell with GPS navigation, ready to find cancer cells and launch suicide attacks at the same time!
3: A cikin al'adun in vitro, an faɗaɗa yawan adadin ƙwayoyin CAR-T. Gabaɗaya, majiyyaci yana buƙatar biliyoyin ko ma dubun-dubatar ƙwayoyin CAR-T (mafi girman girman jiki, ana buƙatar ƙarin sel).
4: Ƙwayoyin CAR-T da aka faɗaɗa ana mayar da su ga mai haƙuri.
5: Kusa da kulawa da marasa lafiya, musanman halayen tashin hankali na jiki yan kwanaki da suka wuce (za'a bayyana dalilin daga baya), kuma a gama aikin.
Inganta tsarin samar da kwayar halitta
Yadda ake samar da ƙwayoyin CAR-T na duniya don rage farashin samarwa babban ƙalubale ne. Wata hanya mai yuwuwa ita ce samun ƙwayoyin T daga masu ba da gudummawa, buga fitar da kwayar halittar HLA na sel, da bayyana ƙwayoyin HLA waɗanda ba na al'ada ba don hana ganowar kwayar halitta mai tsaka-tsakin kisa da ƙwayoyin sel, ta haka ne ke samar da samfurin T cell na duniya. Bugu da ƙari, ƙila ba lallai ba ne a haɗa kwayar halittar CAR a cikin ƙwayoyin chromosomes na ƙwayoyin T, kamar yadda bayanin wucin gadi na CAR ya canza tare da RNA kuma yana aiki a cikin ƙirar dabba. Don ƙarin aminci, ana ba da shawarar kafofin watsa labarai marasa magani.
Kwanan nan FDA ta haɓaka kuma ta wallafa daftarin jagororin don samfurin kwayar halitta da samfuran warkewa, ɗayansu yana buƙatar masana'antun don ƙayyade alamun ayyukan waɗannan ƙwayoyin ko kayayyakin maganin jinsi. Don kwayoyin halittar T da aka canza su, akwai dalilai da yawa waɗanda zasu iya alaƙa da aiki, gami da ɗaukar jigilar jini, yanayin al'adu, tsarin CAR, nau'in tantanin halitta, da kuma yanayin nau'in kwayar. A halin yanzu, mai nuna alama mafi sauki na aiki shine adadin ƙwayoyin CAR +. Koyaya, ainihin nau'in tantanin halitta na iya zama mahimmanci mahimmanci ga aiki. Misali, tsawon rai na ƙwayoyin ƙwaƙwalwar ajiya, ƙwayoyin CD8 +, na iya zama mai nuna alama na aiki. Yawancin masu bincike a halin yanzu suna mai da hankali kan ƙwayoyin T waɗanda aka samo daga jinin gefe. Wasu masu bincike sunyi amfani da CAR na ƙarni na biyu don jujjuya ƙwayoyin halitta.
Kuna so karanta: CAR T-Cell far a Indiya
CAR T-Cell fa'idodi don maganin cututtukan cututtukan jini
A cikin shekaru biyar da suka gabata, ingantaccen ingancin CAR-T ya ci gaba da zama kanun labarai na wasu cibiyoyin bincike. Saboda akwai sanannun maganganun antigen a kan membranes na jini, kuma yana da sauƙi don samun leukocytes da kwayoyin T na halitta a gida ga gabobin jini (kamar jini, kasusuwa, da lymph nodes), an fara amfani da kwayoyin CAR-T don magance su. m cutar sankarar bargo. Mamaki.
CAR-T cells are also the most used clinical trials for hematological malignancies. The results of these clinical trials indicate several key factors that may affect the efficacy of CAR-T cell therapy. For example, although all diseases can express CD19, m lymphoblastic cutar sankarar bargo appears to have a higher response rate than chronic lymphocytic leukemia or indolent lymphoma. The reasons may include patients with lymphoma have T cell defects, tumor microenvironment inhibition, previous treatment, the patient’s age and T cell activity and components (such as the ratio of CD4: CD8, the content of regulatory T cells). The tumor microenvironment may also affect the function of CAR-T cells to dissolve tumor cells. By analyzing CAR-T cells isolated from tumor tissue, they found that they express PD-1, so the therapeutic effect may be affected by PD-L1. Checkpoint blocking technology can increase T cell viability. Application of lymphatic attrition and injection of lymphokines can support the in vivo expansion and survival of imported T cells.
Yana da mahimmanci a fahimci mahimman halayen ayyukan CAR-T. Maganar CAR akan saman tantanin halitta babu shakka yana da mahimmanci. Na biyu, dole ne a gano isassun ƙwayoyin CAR-T a cikin jini bayan dasawa. Ana iya gano ƙwayoyin CAR-T ta hanyar amsawar sarkar polymerase da cytometry mai gudana. Ba a san menene mafi ƙarancin adadin ƙwayoyin CAR-T da ake buƙata don yin tasiri ba. Idan ana iya fadada ƙwayoyin CAR-T yadda ya kamata a cikin vivo, to ƙaramin adadin ƙwayoyin CAR-T na iya haifar da sakamako mai kyau. Bisa la'akari da rikitarwa na samar da ƙwayoyin CAR-T, yana da ban sha'awa sosai don samun damar samun sakamako na warkewa a ƙananan ƙwayar sel. Babu shakka cewa ƙwayoyin da aka shigo da su dole ne su tsira da isasshen lokaci. Dangane da motsin motsin ƙwayar ƙwayar ƙwayar cuta da aka lura, ƙwayoyin da aka dasa suna buƙatar rayuwa a cikin vivo na aƙalla watanni da yawa. A gefe guda, idan an yi amfani da ƙwayoyin CAR-T kawai a matsayin magani na wucin gadi don dashen kasusuwa na kasusuwa, to suna iya buƙatar kawai su wuce na 'yan makonni. Babu wani binciken asibiti na bazuwar da zai tabbatar da cewa ƙwayoyin CAR-T na iya maye gurbin dashen kasusuwa. Amma aƙalla marasa lafiya waɗanda ba su dace da dashen kasusuwan kasusuwa ba za su iya samun dashen tantanin halitta na CAR-T.
Toxicity and adverse reactions mainly include cytokine release syndrome, macrophage activation syndrome, hemophilic linzoma and B cell hypoplasia. Ciwon saki na Cytokine is often accompanied by high levels of IL-6 secretion and leads to macrophage activation syndrome. Although it can be clearly assumed that CAR-T cells can directly kill tumor cells, it is not completely clear which cells produce a large number of cytokines, especially IL-6 (a key factor for toxic response). It is also unclear whether general immunosuppression of anti-cytokine antibodies or steroid hormones can affect anti-tumor responses. IL-6 may be produced by dead B cells, dead tumor cells, or macrophages recruited to lyse tumor cells. It is still unclear whether the severity of cytokine release syndrome or macrophage activation syndrome is related to the anti-tumor effect. The relatively rare adverse reactions include slow response, epilepsy, aphasia, changes in mental state, etc. These are reversible. Macrophage activation syndrome is often associated with neurological toxicity. B cell hypoplasia is the expected result of CD-19 Tarurrukan ci gaba and can be used as an indicator of the survival and effectiveness of CD-19 targeted CAR-T cells in vivo. B cell hypoplas
ana iya allurar ia da glycinin a matsayin ƙarin magani. Ciwon hypoplasia na B mai ɗorewa, koda tare da hanyoyin maye gurbin, na iya haifar da haɗarin kamuwa da cuta. Kwayoyin B zasu iya murmurewa bayan kwayoyin CAR-T sun ɓace a cikin jiki, don haka marasa lafiya na iya karɓar ƙwayoyin CAR-T kuma. Yayinda yawancin marasa lafiya ke karɓar maganin ƙwayar CAR-T, bincike na asibiti ya kamata ya mai da hankali kan nazarin halayen mai guba da hanyoyin sarrafa su, gami da toshewar cytokine, steroids, da lokaci mafi kyau da kuma ƙimar haɓakar sunadarin rigakafi.
Saboda mahimmancin guba da ke cikin ƙwayoyin CAR-T, masu bincike sun kuma gwada dabaru don haɗa ƙwayoyin halittar kashe kansa a cikin ƙwayoyin halitta ko kashe bayyana jinsi. Koyaya, har yanzu yana da wahala a haɗa tsarin kwayar halittar kashe kansa cikin dukkanin ƙwayoyin CAR-T, saboda yawancin kwayar halittar kashe kanta suna da rigakafi (alal misali, kwayar cutar ta herpes simplex dake bayyana thymus kinase) ko kuma abubuwan da ke haifar da kashe kansa yakamata a gudanar dasu ta hanji. Bugu da ƙari, ana iya canza homing T-cell ta hanyar magana mai wucewa na masu karɓar maganin ko kuma hana amfani da magani na masu karɓar maganin a matsayin dabarun haɓaka inganci da rage yawan guba.
Abubuwan farin ciki na CAR T-Cell far
There are two main obstacles in expanding the application of CAR-T cells beyond B-cell malignancies: finding new targets and mass production. Potentially promising targets include CD30 (for the treatment of Hodgkin’s disease and fungoides mycosis), immunoglobulin Gκ light chain (for the treatment of B-cell leukocytes), CD33 and Lewis-Y (acute myeloid leukemia), CD123 and CD44v6 (Acute myeloid leukemia and myeloma), CD19 (B cells), CD23, and ROR1 (chronic lymphocytic leukemia). New targets under study include BCMA, CD70, CD74, CD138 and CS1 (see table below). Currently, pharmaceutical companies, biotechnology companies, universities, and cooperative organizations are conducting CAR-T cell research. This is an exciting period for the treatment of all hematological malignancies; ten years ago, few people expected that the hope of modifying gene therapy would be realized by CAR-T cells for the treatment of hematological malignancies.
Faxar Cancer shine gidan yanar gizo na farko na gida don gudanar da bincike da kuma tuntuɓar maganin cutar kansa a duniya. Yana aiki tare da fiye da 30 na duniya cutar sankara da cibiyoyin kula da magani da kuma fiye da 300 masana a gida da waje don ba da shawarwari na ƙwararrun oncology da shawarwari ga marasa lafiya na cikin gida don taimakawa marasa lafiya don karɓar mafi kyawun gwajin kwayoyin halitta, magunguna, fasaha da jiyya na gwaji na asibiti. an daidaita shi kuma an daidaita shi.
