8/30/2023 0 Comments Qcart trial![]() ![]() These include (1) virus-associated safety concerns (2) limited payload capacity of viral vectors (3) low expansion capacity and low percentage of CAR + T cells following transduction (4) low CAR-T cell persistence and (5) high cost of manufacturing virally-produced CAR-T cells.Ī virus-free system can overcome most if not all of these hurdles, but electroporation-associated damages in virus-free systems present a critical challenge. However, CAR-T cells generated virally have several limitations. 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 demonstrated 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 and low level of senescence and exhaustion ( Figure 1). T SCM 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 a 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 cost associated with CAR-T cell manufacturing. 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. ![]()
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