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To be sure, the CD19-CART cell therapy technology should be individualized, but in addition to the CAR T design itself that will affect the treatment effect, the timing of application, the patient's basic condition, the dose of infusion, etc., will have a significant impact on the clinical effect. Different car gene vectors affect CART cell function, and currently used vectors are gamma retroviruses, lentiviruses, and car t plasmid. Even if the CAR structure is the same, the CART cells cultured by different research centers will be very different. In the composition of the new generation of CAR, a co-stimulation region was added, and in particular, the addition of CD28 or CD137 in the costimulatory region resulted in the proliferation of cells in vivo and the anti-tumor activity was significantly enhanced.<br>
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www.creative-biolabs.com/car-t Summary of Existing Problems in CART Therapy
1 CAR-T Therapy Background To be sure, the CD19-CART cell therapy technology should be individualized, but in addition to the CAR T design itself that will affect the treatment effect, the timing of application, the patient's basic condition, the dose of infusion, etc., will have a significant impact on the clinical effect. Different car gene vectors affect CART cell function, and currently used vectors are gamma retroviruses, lentiviruses, and car t plasmid. Even if the CAR structure is the same, the CART cells cultured by different research centers will be very different. In the composition of the new generation of CAR, a co-stimulation region was added, and in particular, the addition of CD28 or CD137 in the costimulatory region resulted in the proliferation of cells in vivo and the anti-tumor activity was significantly enhanced.
2 Related Studies Introduction Xu et al. analyzed the clinical trials in 5 centers and summarized the factors that could improve the efficacy of CART cells: pretreatment of lymphocyte removal, IL-2 infusion, duration of CART cells ≥ 4 weeks, and peak of peripheral blood CART cells ≥ 0.1%; The peak of IFN-γ was ≥200pg/ml; however, the number of infused T cells and the ratio of CD4+/CD8+ were not significant. Therefore, based on these factors, we can take corresponding improvements to improve the efficacy, including the car t cell structure, from the first to the fourth generation of the promotion; pretreatment and cytokine application before infusion; gene transduction from retrovirus to lentiviral vector and so on. The relationship between adverse reaction intensity and efficacy is also a problem that needs to be studied. The time of onset of symptoms and the severity of CRS depend on the inducing drug, the degree of immune cell activation, and the tumor burden.
Most of the studies have shown that chemo-removal of lymphocytes in vivo before reinfusion can enhance anti-tumor effects. Porter et al successfully used CART cells to successfully treat 3 patients with CLL and found that cytokines such as IFN-γ, CXCL9, IL-6 and soluble IL-2 receptors were significantly increased after CART cells were transfused into the body, and peaked on the 23rd day after input. The increase in cytokines in the bone marrow is consistent with the reduced level of leukemic cells. The number of CART cells is consistent with the time of onset of tumor lysis syndrome and the elevated level of cytokines. To reduce adverse reactions, it is necessary to carefully select targeted antigens, and to determine the most effective and safe dose through dose escalation studies.
3 Conclusion The use of CART cells to specifically target CD19-positive B-cell lymphoma and leukemia patients has achieved significant clinical results and is expected to be widely used. Although CART therapy is currently conducted for a relatively short period of time, there is still a lack of large-scale samples, and many adverse reactions and complications need to be gradually discovered and resolved in clinical trials. However, in the clinical trials reported for the treatment of B-cell lymphoma and leukemia, CART showed a very significant effect, especially for relapsed and refractory patients, thus providing a basis for a larger-scale, multi-center clinical study.
4 About Us About Creative Biolabs As a global company, Creative Biolabs has more than 200 talented and well-trained scientists located in different continents working closely with partners from the entire world to develop and produce medicines of tomorrow. Specifically, we are the established leading expert in TCR and CAR T&NK cell immune therapy development, as we offer the one-stop custom services that cover the entire new drug development pipeline. Additionally, we also offer an exclusive line of ready-to-use TCR and CAR T&NK cell construction products, such as virus packaging, purification, expansion and titer determination kits. Furthermore, we have built up a unique unparalleled CAR construction and production platform for all four CAR generations.
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