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The patient’s T-cells are genetically modified in laboratories to include chimeric antigen receptors (CARs). The CARs are designed to recognize the specific cancer antigens and bind to them, allowing T-cells to target and attack the cancer cells. The genetically modified T-cells are administered back to the patients as a treatment.
The T-cells can optionally be modified in various ways, cultured and infused into patients. T cells can be modified via genetic engineering, producing CAR-T cell or TCR T cells or by exposing the T cells to tumor antigens in a non-immunosuppressive environment, that they recognize as foreign and learn to attack.
Each T cell's TCR is specific to one antigen and sits on the T cell's surface. The affinity of human TCRs to tumor antigens is relatively low, rendering them unable to recognize and kill tumor cells effectively. The modified T cell has much higher affinity, which enhances both recognition and affinity supporting the recognition of tumor cells. [1]
The CAR programs the T cells to target an antigen present on the tumor cell surface. For safety, CAR T cells are engineered to be specific to an antigen that is expressed on a tumor cell but not on healthy cells. [2] After the modified T cells are infused into a patient, they act as a "living drug" against cancer cells. [3]
Alternatively, Genetically engineered T cells are created by harvesting T cells and then infecting the T cells with a retrovirus that contains a copy of a T cell receptor (TCR) gene that is specialised to recognise tumour antigens. The virus integrates the receptor into the T cells' genome. The cells are expanded non-specifically and/or stimulated.
T cell Efficacy of treatment highly depends on whether infused cells can persist within patients. Increasing the T - cell persistence has been a major challenge and direction for TCR therapy. [7] Tumor microenvironment Tumor microenvironments are usually immunosuppressive. They attract immunosuppressive cells and promote cancer cell survival.
In early trials, preparing engineered T cells cost $75,000 to manufacture cells for each patient. [4] Interleukin-2 is normally added to the extracted T cells to boost their effectiveness, but in high doses it can have a toxic effect. The reduced number of injected T cells is accompanied by reduced IL-2, thereby reducing side effects.
Idecabtagene vicleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. [ 4 ] [ 7 ] Each dose is customized using a patient's own T-cells, which are a type of white blood cell, that are collected and genetically modified to include a new gene that facilitates ...
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