![]() The majority of existing approaches are based on non-specific or antigen-presenting/feeder cell-based protocols. One of the significant challenges in chimeric antigen receptor-modified T cells (CAR-T) therapy is obtaining an adequate number of CAR-T cells with the desired function through donor T cell stimulation and expansion in vitro. ![]() It is predicted that this new methodology will significantly advance the ability to obtain improved populations of functional CAR-T cells for therapy. The data presented in this article clearly demonstrate that this protocol produced antigen-specific vesicles with the capacity to induce stronger stimulation, proliferation, and functional activity of CAR-T cells than is possible with existing protocols. This novel approach is to make antigenic microcytospheres from common cell lines stably expressing surface-bound CAR antigens, and then use them for stimulation and expansion of CAR-T cells. To develop a specific and improved protocol for CAR-T cell expansion, cell-derived membrane vesicles are taken advantage of, and the simple structural demands of the CAR-antigen interaction. Modern protocols for CAR-T cell expansion are imperfect since non-specific stimulation results in rapid outgrowth of CAR-negative T cells, and removal of feeder cells from mixed cultures necessitates additional purification steps. This step is challenging, especially if non-viral low-efficiency delivery protocols are used to generate CAR-T cells. ![]() Manufacturing of therapy-competent functional CAR-T cells needs robust protocols for ex vivo/in vitro expansion of modified T-cells. Development of CAR-T therapy led to immediate success in the treatment of B cell leukemia.
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