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Immune Organoids to Study Antigen Presentation

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Abstract

Vaccine and immunotherapy development needs to be timely to provide treatments for infections and cancer. Current platforms for testing vaccines and immunotherapies are limited to cell cultures with little physiological relevance or animal models that have species-specific responses. Likewise, cancer drugs and signaling pathways are evaluated in cell cultures without key environmental cues or stromal support. To address these limitations, we developed immune organoids that recapitulate aspects of lymph nodes and spleen to study antigen presentation in immune tissues and drug response of malignant immune cells. We highlighted existing immune organoid models and vaccine adjuvants. To investigate materials suitable for immune organoids, we compared the effect of PEG endpoint chemistry and mechanoreceptor integrin ligands on B cell maturation. Incorporating immune organoids in models of malignant immune cells, we showed that lymphomas were susceptible to drugs in an extracellular matrix and stromal cell-dependent manner. To study the mode of antigen presentation, we engineered and compared cell-based and artificial polymeric bead-based antigen presenting cells. Inspired by the particle-based presentation of protein antigens, we developed an immunomodulatory nanogel that enhance immune response in animal models and immune organoids. Finally, we presented potential ideas to further improve of immune organoids. In the long term, immune organoids can be used to develop vaccines and immunotherapies.

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93 pages

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2021-12

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Keywords

Germinal center; Immune; Lymphoma; Nanovaccine; Organoid

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Committee Chair

Kirby, Brian

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Singh, Ankur
Xu, Chris

Degree Discipline

Mechanical Engineering

Degree Name

Ph. D., Mechanical Engineering

Degree Level

Doctor of Philosophy

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Government Document

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dissertation or thesis

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