CAR-T CELL THERAPY (part4)
2.9 Safety
Due to the injection of CAR-T cells into the body, it creates some side effects. these are cytokine release syndrome and neurological toxicity. There is little data on the long-term effects of CAR-T cell therapy, as it is a new therapy. When the CAR-T cell recognizes the healthy antigen, it can express it in non-pathogenic tissue. Excessive toxicity may occur due to this unfavorable situation because it attacks the wrong tissue [19,23]. The most common problem after treatment with CAR-T cells is cytokine release syndrome (CRS). CRS is when the immune system is activated, it releases an increasing number of inflammatory cytokines. The clinical manifestation of this syndrome is similar to sepsis with high fever, fatigue, myalgia, nausea, capillary leaks, tachycardia and other cardiac dysfunctions, hepatic failure and renal failure [21]. CRS occurs in almost all patients treated with CAR-T cell therapy; in fact, the presence of CRS is a diagnostic marker that CAR-T cells are working towards killing cancer cells. however, greater severity of CRS may result in higher disease burden. Neurological toxicity can also be seen in CAR-T cell therapy. The underlying mechanism is not fully understood and may or may not be associated with CRS. Clinical manifestations include delirium, partial loss of coherent speech while having the ability to interpret language (expressive aphasia), low alertness (obtundation), and seizures [19].
2.10 Economy
The cost of CAR T cell therapies has been criticized, with initial costs of tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) being $375,000 and $475,000, respectively. The high cost of CAR T therapies is due to complex cellular production in specialized Good Manufacturing Practice (GMP) facilities and the high level of hospital care required after CAR T cells are administered due to risks such as cytokine release syndrome. In the United States, CAR T cell therapies are covered by many private insurance companies [24].
3. Conclusion
Although the initial results of CAR -T cell therapies are impressive, this treatment approach still has room for development in many respects. A priority for future studies is to better understand the significance of CAR -T cell persistence. The goal of therapy is to achieve sustained, ideally permanent, remission of disease in patients, and two general hypotheses may explain how CAR -T cell therapy can achieve this goal. First, a strong CART cell response eliminates all malignant cells immediately after infusion, so long-term cell persistence is not required. Second, a limited number of malignant cells are eliminated, so long-term CAR -T cell persistence is required. Indeed, CAR -T cell continuity is more important in the tumor area than in the circulation, and activation-induced cell death (AICD) is an important factor limiting CAR -T cell survival. Immunological rejection against peptides and amino acids in the structure of CARs, loss of expression of the target antigen, defined as "antigen escape", and of course very high treatment costs are other limiting points of CAR -T cell therapy. Adaptive T-cell transfer has been used to treat malignancies and can be considered a biopharmaceutical for cancer treatment. A biopharmaceutical is defined as a product that is originally natural or derived from biological sources with industrial additives. The main goals of T-cell engineering are to target tumor antigens and increase antitumor functions. CAR T-cell therapies are powerful breakthrough treatments, but several challenges remain to be overcome. The optimal design of CARs remains an area of research. To be of benefit in other disease types, tumor-specific targets in solid tumors need to be identified. Adoptive immunotherapy with CAR T cells has proven successful in clinical trials, and the ultimate goal is to induce immunity that is resistant to disease progression without severe side effects. Whether this treatment option will replace or serve as a bridge to HSCT in the near future remains an open question. For the treatment to be used routinely, automation and robotic culture techniques should be used instead of manual cell culture techniques in the production process.
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