Alginate Core-Shell Scaffolds for CAR T cell Manufacturing

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Mousavi Karimi, Zahra
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Cancer patients with advanced-stage disease develop resistance to traditional therapies such as chemotherapy and radiation therapy, leading to the necessity of a novel technology that is both specific and efficient to the patient’s cancer. Genetically engineered T cell receptors can recognize and bind to antigens expressed on tumor cells and kill them. As a result, T cell immunotherapies have been established as a new strategic cancer therapy. The promising success of T cell immunotherapies for treatment of cancer and other diseases demonstrate the need for scalable manufacturing processes for product commercialization. Unlike traditional chemotherapies, cell-based immunotherapies are composed of living entities, and hence they are different in their development, properties and regulatory pathways in comparison to traditional drugs, which are simple chemicals. Current T cell manufacturing techniques are complicated processes that do not account for the complexity of the lymph nodes, where T cells expand rapidly in response to disease. Consequently, it is difficult to produce enough cells for quality control assays and meet the Good Manufacturing Practices (GMP) guidelines. Thus, we hypothesize that creating a novel microenvironment that can mimic the lymph nodes will enhance expansion of T cells and allow this promising treatment to reach more patients in the clinic. To do so, we proposed using alginate which has been widely used for cell encapsulation. We prepared and optimized alginate core-shell scaffolds to provide an environment for close cell-cell contact and communication as well as protect T cells against stress for CAR T cell signaling and expansion. After expansion, the scaffolds were dissolved through both enzymatic and physical dissociation. This method will eventually allow the modified T cells to be placed in a bioreactor, allowing this technique to be commercialized by companies in the cell manufacturing industry.
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