T cells are the main weapon of the immune system, which can effectively identify and kill infected cells, and if cancer cells are identified, they will also kill them. However, tumor cells will disguise themselves so that T cells cannot recognize them. We can identify disguised cancer cells and kill them by installing T cells in the positioning system -CAR.
Now let's learn about CAR-T therapy that can treat B-cell tumors. Because B cells express CD 19, CD 19 CAR-T therapy can effectively treat B cell line tumors.
CD 19 is a CD molecule (differentiation cluster) expressed by B cells. All B cell lines except plasma cells, malignant B cells and FDC (follicular dendritic cells) express this molecule? . It is an important membrane antigen involved in the proliferation, differentiation, activation and antibody production of B cells, and can also promote the signal transduction of BCR.
CD 19 is a type I transmembrane protein with a single transmembrane domain, an intracellular C-terminal and an extracellular N-terminal. The extracellular domain contains two C2 immunoglobulin-like domains. The intracellular domain is highly conserved and consists of 242 amino acids and 9 tyrosine residues near the C- terminal. Many studies show that the biological function of CD 19 depends on three cytoplasmic tyrosine residues: Y39 1, Y482 and Y5 13.
CD 19 plays a synergistic receptor role in B cell activation and signal transduction, regulates B cell activation and proliferation, participates in the signal transduction function of B cells, and mediates T cells to kill target cells.
CD 19, CD2 1, four transmembrane proteins CD8 1(TAPA- 1) and CD225*** form a signal transduction complex. CD 19 complex reduces the threshold of BCR-mediated B cell activation by regulating endogenous and receptor-induced signals. Thereby promoting the production of autoantibodies and forming corresponding immunopathological injuries.
CD 19 is considered to play a dual role in B cell activation. First of all, it plays the role of an adaptor protein, and collects the signal proteins in the cytoplasm onto the membrane. Secondly, when combined with BCR, as a signal subunit of CD 19/CD2 1 complex, complement enhances B cell activation through BCR-CD 19/CD2 1 binding.
CAR-T therapy is chimeric antigen receptor T cell immunotherapy, and its full name in English is chimeric antigen receptor T cell immunotherapy. This is a new method to treat tumors accurately. In recent years, through optimization and improvement, good results have been achieved in clinical tumor treatment. It is a very promising new method of tumor immunotherapy, which can treat cancer accurately, quickly and efficiently.
In the laboratory, technicians activated T cells through genetic engineering technology, installed a positioning navigation device CAR (tumor chimeric antigen receptor), and transformed ordinary "warrior" T cells into "super warrior", that is, CAR-T cells. He used his positioning navigator CAR to specifically identify tumor cells in vivo, and released a large number of various effector factors through immune action, which can effectively kill tumor cells, thus achieving the purpose of treating malignant tumors.
1) to evaluate whether the patient meets the indications for CAR-T treatment.
2) Separation of T cells: Monocytes were separated from the blood of tumor patients by a peripheral blood blood cell separator, and then T cells were further purified by magnetic beads.
3)T cell transformation: The virus vector containing chimeric antigen receptor which can recognize tumor cells and activate T cells is transformed into T cells by genetic engineering technology, that is, T cells are transformed into CAR-T cells.
4) expanding CAR-T cells: a large number of expanded CAR-T cells were cultured in vitro. Generally speaking, a patient needs tens of millions or even hundreds of millions of CAR-T cells. The heavier he is, the more cells he needs.
5)CAR-T cells are reinfused into human body: the amplified CAR-T cells are reinfused into the patient's body through veins to start tumor cell immunotherapy.
6) Monitoring reaction: closely monitor the patient's physical reaction, especially the serious adverse reactions that may occur within one to two weeks after cell infusion.
7) Evaluation of curative effect: Evaluate the curative effect of the primary disease on day 15 and 30 after CAR-T cell infusion.
The whole course of treatment lasts about 5 weeks, and the first step to the third step takes 2 weeks, which takes a long time.
CAR-T therapy undoubtedly brings new hope for cancer treatment. However, this therapy also has serious adverse reactions, mainly cytokine release syndrome (also known as cytokine release storm, CRS) and neurotoxicity. If it is not handled in time, it may be life-threatening. Therefore, CAR-T cells must be closely monitored after transfusion.
Cytokine release syndrome (CRS) occurs because a large number of CAR-T cells are imported into the body, which leads to the activation of the immune system and the release of a large number of inflammatory cytokines, thus causing serious adverse reactions. The clinical manifestations of the syndrome include: high fever, chills, nausea, fatigue, muscle pain, capillary leakage, systemic edema, flushing, hypotension, oliguria, tachycardia, cardiac insufficiency, dyspnea, respiratory failure, liver failure, renal insufficiency and so on.
The clinical manifestations of neurotoxicity include headache, partial loss of language ability, slow response, seizure, coma and so on. And even died of brain edema. Allergic reactions are also foreseeable adverse reactions.
Ren Messi? | ? Official documents and letters