Chii chinonzi CAR T-Cell kurapwa?
CAR T-Cell kurapa, whose full name is Chimeric Antigen Receptor T-Cell Immunotherapy,. This is a new type of cell therapy that has been used for many years, but has only been improved and used clinically in recent years. Similar to other immunotherapy, its basic principle is to use the patient’s own immune cells to clear cancer cells, but the difference is that this is a cell therapy, not a drug.
Maitiro eCAR T-Cell kurapa
1: Tsaura immune T masero kubva kune vane cancer.
2: Using genetic engineering technology to add a chimeric antibody that recognizes tumarara 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: In in vitro culture, a large number of CAR-T cells are expanded. Generally, a patient needs billions or even tens of billions of CAR-T cells (the larger the body size, the more cells are required).
4: Masero eCAR-T akawedzerwa anodzorerwa kumurwere.
5: Nyatsoongorora varwere, kunyanya kuita kwechisimba kwemuviri mazuva mashoma apfuura (chikonzero chicha tsanangurwa gare gare), woita kuti basa riitwe.
Gadziridza maitiro ekugadzira maseru
Maitiro ekugadzira ese eCAR-T maseru kudzikisa mutengo wekugadzira idambudziko guru. Imwe nzira inogoneka ndeyekuwana maT masero kubva kune vanopa, kugogodza iyo HLA gene yemaseru, uye kuratidza asiri ekirasi HLA mamorekuru kudzivirira mhondi yakasikwa cell-mediated cell recognition uye cell lysis, nekudaro kugadzira T cell chigadzirwa. Mukuwedzera, zvingave zvisingadikanwi kubatanidza CAR gene mumakromosomes eT masero, sekutaura kwenguva pfupi kweCAR yakashandurwa neRNA inoshandawo mumhando dzemhuka. Kuti uwedzere kuchengeteka, serum-yemahara midhiya inokurudzirwa.
Iyo FDA ichangoburitsa uye yakaburitsa madhairekitori edzidziso esero uye geni ekurapa zvigadzirwa, imwe yacho inoda kuti vagadziri vaone zviratidzo zvezviitiko zveaya maseru kana zvigadzirwa zvemagen'a ekurapa. Kune maT T maseru, pane zvinhu zvakawanda zvinogona kunge zvine chekuita nebasa, kusanganisira mutakuri wegene, mamiriro etsika, chimiro CAR, sero mhando, uye chiyero cherudzi rwechitokisi. Parizvino, chinongedzo chakareruka che chiitiko chehuwandu hwemasero eCAR +. Nekudaro, iyo chaiyo mhando yesero inogona kunge yakakosha zvakaenzana pakuita. Semuenzaniso, kurarama kwenguva refu kwepakati memusoro maseru, CD8 + maseru, inogona kuve chiratidzo cheicho chiitiko. Vazhinji vaongorori parizvino vanotarisa masero eT anotorwa muropa remupendero. Vamwe vaongorori vakashandisa chizvarwa chechipiri CAR kutapudza maseru anouraya chaiwo.
Unogona kuda kuverenga: CAR T-Cell kurapa muIndia
CAR T-Cell kurapa zvakanakira kurapwa kwehematological malignancies
Mumakore mashanu apfuura, kushanda zvakanaka kweCAR-T kwakaramba kuri misoro yemamwe masangano ekutsvagisa. Nekuti kune akawanda anozivikanwa maantigen ekutaura pamasero eropa, uye zviri nyore kuwana leukocytes uye T masero anogara kumba kune nhengo dzeropa (seropa, bone marrow, uye lymph nodes), masero eCAR-T anotanga kushandiswa kurapa. malignant leukemia. Akashamisika.
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, acute lymphoblastic leukemia 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.
Izvo zvakakosha kuti unzwisise akakosha maitiro eCAR-T cell chiitiko. Kutaura kweCAR pane cell surface hakuna mubvunzo kwakakosha. Chechipiri, masero eCAR-T akakwana anofanirwa kuonekwa muropa mushure mekusimwa. Masero eCAR-T anogona kuonekwa ne polymerase chain reaction uye flow cytometry. Hazvizivikanwe kuti chiyero chidiki chemasero eCAR-T chinodiwa kuti chishande. Kana masero eCAR-T anogona kunyatsowedzerwa mu vivo, ipapo masero maduku eCAR-T anogona kuramba achibudisa migumisiro yakanaka. Tichitarisa kuoma kwekugadzira masero eCAR-T, zvinoyevedza kuti ugone kuwana mhedzisiro yekurapa padanho rakaderera remasero. Hapana mubvunzo kuti maseru anounzwa kunze kwenyika anofanira kurarama nguva yakakwana. Zvichienderana nekinetics yebundu cell clearance yakacherechedzwa, masero akaisirwa anofanirwa kurarama mu vivo kweinenge mwedzi yakati wandei. Kune rumwe rutivi, kana masero eCAR-T achingoshandiswa senzira yekushandura yemapfupa ekugadzirisa mapfupa, saka angangoda kugara kwemavhiki mashomanana. Iko hakuna chidzidzo chekiriniki chisingaverengeki kuratidza kuti masero eCAR-T anogona kutsiva mwongo kuisirwa. Asi vangangoita varwere vasina kukodzera kuisirwa mwongo vanogona kugamuchira CAR-T cell transplantation.
Toxicity and adverse reactions mainly include cytokine release syndrome, macrophage activation syndrome, hemophilic lymphoma and B cell hypoplasia. Cytokine kuburitsa chirwere 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 yakanangwa kurapwa and can be used as an indicator of the survival and effectiveness of CD-19 targeted CAR-T cells in vivo. B cell hypoplas
ia inogona kubaiwa ne glycinin semushonga wekuwedzera. Kuenderera mberi kweB-cell hypoplasia, kunyangwe nekurapa kwekutsiva, kunogona kukonzera njodzi yekuwedzera yehutachiona. Masero eB anogona kupora mushure mekunge masero eCAR-T anyangarika mumuviri, saka varwere vanogona kugamuchira maseru eCAR-T zvakare. Sezvo varwere vazhinji vachigamuchira CAR-T cell therapy, tsvakiridzo yekiriniki inofanirwa kutarisisa pakudzidza kwechepfu uye maitiro avo ekutonga, anosanganisira cytokine blockade, steroids, uye yakakwana nguva uye dosi yeimmune protein yekuwedzera.
Nekuda kwehusimbe hwakakomba hwemasero eCAR-T, vaongorori vakaedzawo nzira dzekubatanidza majeni ekuzviuraya mumasero kana kudzima kutaura kwemajini. Zvisinei, zvichiri kunetsa kubatanidza kuzviuraya kwemajini mumaseru ese eCAR-T, nekuti mazhinji maitiro ekuzviuraya majini ane immunogenic (semuenzaniso, herpes simplex virus inoratidzira thymus kinase) kana mishonga inokurudzira kuzviuraya inofanirwa kuiswa mukati. Uye zvakare, iyo T-cell homing inogona kuchinjika neyekupedzisira kutaura kwe chemokine receptors kana iyo pharmacological blockade ye chemokine receptors inogona kushandiswa senge zano rekusimudzira kushanda uye kudzikisira huturu.
Tarisiro inonakidza yeCAR T-Cell kurapwa
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 mycosis fungoides), 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.
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