In the laboratory, technicians activate the T cells through genetic engineering technology and load them with the localization navigation device CAR (tumor chimeric antigen receptor), transforming the T cells, which are ordinary warriors, into super warriors, i.e. CAR-T cells. T-cells are transformed from ordinary "warriors" into "super warriors", i.e. CAR- cells, which use their "localization navigation device" CAR to specifically identify tumor cells in the body and release a large number of multiple effectors through immunity, which can efficiently kill tumor cells, thus achieving the purpose of treating malignant tumors.
The advantages of CAR-T 01 fast-acting CAR-T cells are genetically engineered to modify the patient's own T lymphocytes to express chimeric antigen receptor (CAR), which is able to effectively overcome the immune escape of tumor cells through the down-regulation of the expression of the MHC molecule and the reduction of the antigen presentation, so that the tumor cells have nothing to run away from.02 high remission rate CAR-T drugs are different from other drugs, including antibody drugs, ADCs, recombinant proteins and other drugs. CAR-T drug is a new type of therapeutic means different from traditional biological drugs including antibody drugs, ADC, recombinant proteins, etc. It has the characteristics of "living drug", and its therapeutic depth and continuity are not available in the above traditional biological drugs. B38M have a remission rate of 94% and 100%, respectively.03 Long remission timeAntibody-mediated antitumor drugs can only kill tumor cells with high expression of cell surface antigens, whereas CAR-T can effectively kill tumor cells with low expression of cell surface antigens, with a much deeper depth of response.CAR-T Side Effects01 Cytokine storm (CRS) Due to the proliferation of a large number of T-cells, which results in cytokines being The release of cytokines due to massive proliferation of T-cells causes the body to experience fever, myalgia, hypotension, respiratory failure, etc. These adverse reactions are CRS, and for the cytokine storm caused by the infusion of CAR-T cells, IL-6 receptor antagonist drugs can be utilized for treatment in the clinic.02Targeted cytotoxicity Due to the strong targeting of CAR-T antigens, it is not possible to differentiate between tumor cells and normal cells expressing the corresponding antigen, therefore, CAR-T can not be used for the treatment of tumor cells expressing low levels of antigen. normal cells, so CAR-T will attack both tumor cells and normal cells expressing the corresponding antigen. For example, CAR-T cell therapy targeting CD19 leads to B-cell dysplasia, and CAR-T cells targeting HER2 lead to attacks on other tissues or organs, such as cardiopulmonary systemic toxicity. The solution to this is to design well-targeted CARs to minimize CAR-T damage to normal tissues.CAR-T treatment costCAR-T treatment cost is expensive, 51Dongshi editorial based on the data survey to understand that the total cost of CAR-T treatment is about $400,000 to $500,000 range. However, this is a conservative estimate and is considered by some industry insiders to be much lower than the actual total cost, which can be upwards of $200,000 for CAR-T cell therapy, including the cost of medications, nursing care, intensive care unit costs, and other expenses, as well as the cost of managing some of the side effects.
What cancers can CAR-T treatMost CAR-T therapies are still in clinical trials, in which treatment is focused on:
Relapsed acute B-lineage lymphoblastic leukemia (reoccurring after remission with treatment), or refractory acute B-lineage lymphoblastic leukemia (those that have not remitted with other anti-leukemia treatments). Large B-cell non-Hodgkin's lymphoma that has failed two or more treatments.CD19-positive relapsed, refractory malignant lymphoma.CD19 treatment failure and CD22-positive acute lymphoblastic leukemia.PS: CAR-T therapies have been investigated in clinical trials in other antitumor areas, but the effects are not yet clear.
Patient assessment for CAR-T therapy processEvaluate whether the patient meets the indications for CAR-T therapy. Isolation of T cellsSingle nucleated cells are isolated from the tumor patient's blood by a peripheral blood cell separator, and the T cells are further purified by magnetic beads. Modified T cells are genetically engineered by transferring a viral vector containing a chimeric antigen receptor that recognizes tumor cells and activates T cells into T cells, i.e., the T cells are modified into CAR-T cells. Expanded CAR-T cells are cultured in vitro in order to expand a large number of CAR-T cells, generally a patient needs tens of millions or even hundreds of millions of CAR-T cells, and the larger the body weight, the more cells are needed.CAR-T cells are returned to the bodyThe expanded CAR-T cells are returned to the patient's body through a vein, and the tumor cellular immunotherapy is started. The patient's physical reaction is closely monitored, especially the possibility of severe adverse reactions within one to two weeks after the cells have been infused into the body. Evaluate the treatment effect mostly on the 15th and 30th day after the infusion of CAR-T cells to evaluate the treatment effect on the primary disease.PS: 51Dongshi editor learned that the whole course of treatment lasts about 5 weeks, of which the first step to the third step mentioned above takes 2 weeks, taking a longer time. Factors affecting CAR-T therapy 01 Patient's own condition CAR-T therapy is needed to be able to collect enough high-quality T cells from the patient. Some patients, due to pre-chemotherapy, or very severe disease, the number and quality of T cells in their body cannot meet the T cells needed for CAR-T therapy. In addition, patients with a large tumor load in the brain are also not able to use CAR-T therapy right away, considering the fatal adverse reactions.02 CAR-T manufacturing process and procedureThe CAR-T therapy process is very complicated and high-end, involving screening and collection of T-cells, gene modification, activation, cultivation, expansion, modification and so on, and each step requires careful design and quality control, and any mistake in any step will affect the CAR-T therapy.03 Tumor's own characteristics A study showed that nearly half of the patients' tumors recurred within one year after receiving anti-CD19 and anti-CD22 CAR-T cell therapy, which is highly related to tumor escape and CART persistence. How to find more tumor targets and kill as many tumors as possible, as well as how to increase the persistence of CART in vivo still needs to be improved and developed.04 Adverse reactions to treatment generally have the adverse reaction of cytokine release storm, which indicates that the body responds to the treatment and kills tumors effectively; however, serious adverse reactions often need to take measures in advance to interrupt the killing effect of CAR-T cells in vivo, whether this affects the elimination of tumors or not. action, whether this will affect the final effect of eliminating the tumor remains to be further evaluated.CAR-T faces challenges01Recurrence problemSome patients do not have a sustained response (about 30%~50%), they start out with a response, but soon relapse. This is not only the escape of CD19-negative cancer cells, as CAR-T therapies targeting other targets have also faced relapse in patients in clinical trials, so it seems that there are other factors at play.02 Toxicity IssuesHow to deal with toxicities of CAR-T cell therapies is an unresolved issue at the moment. For grade 3/4 adverse reactions, high-dose steroids are usually given, and sometimes grade 2 neurotoxicity occurs that needs to be dealt with as well, but there is no knowledge of the actual effect of corticosteroids on T cells. The most serious neurotoxic complications are fatal in most cases, and this occurs in only 1% to 2% of patients, making large-scale clinical trials impossible. Recommended reading 01 What are the symptoms of cancer in different body parts? Cancer treatment and prevention of cancer in different parts of the bodyThe topic of cancer is always a heavy heart, medical data show that about 10,000 people are diagnosed with cancer every day in China, and 7 people are diagnosed with cancer every minute...
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