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Viral vector has been widely used for the development of CAR-T cell therapy due to its high efficiency in gene delivery and integration, resulting in stable long-term gene expression. A technological breakthrough needs to be developed to overcome these hurdles. differentiation, exhaustion, senescence and survival). Consistent with these desired therapeutic properties, it has been clinically-proven that high levels of CAR + T SCM cells lead to better clinical outcomes.ĬAR-T cell therapy faces several challenges in the context of solid tumor, including (1) lack of CAR-T cell trafficking to the tumor (2) antigen heterogeneity of solid tumors and (3) immunosuppressive tumor microenvironment (TME) which can adversely affect T cell fitness (e.g. Furthermore, T SCM cells have the highest therapeutic efficacy due to enhanced metabolic fitness as well as low level of senescence and exhaustion ( Figure 1). The T SCM cells are characterized by stem-like properties with high capacity for self-renewal, resulting in long-term persistence. Therefore, the potency and persistence of CAR-T cells are key to successful CAR-T cell therapy. However, the widespread application of CAR-T cell therapy for the treatment of cancer has encountered several challenges, including (1) the potential for on-target off-tumor toxicity and/or cytokine release syndrome (CRS) (2) relapses due to: (i) antigen escape and/or antigen heterogeneity of solid tumor, resulting in outgrowth of non-targeted tumor cells and/or (ii) a lack of CAR-T cell persistence (3) lack of potency for the treatment of solid tumors and (4) the high costs associated with CAR-T cell manufacturing.
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The development of chimeric antigen receptor T (CAR-T) cell therapy is a major breakthrough in cancer therapy due to the remarkable clinical responses observed in certain hematological cancer patients infused with cancer-targeting CAR-T cells.