All ETDs from UAB

Advisory Committee Chair

Xiaoguang Margaret Liu

Advisory Committee Members

Gangjian Qin

Lufang Zhou

Renata Jaskula-Sztul

Wuqiang Zhu

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Cancer treatment is one of the most daunting challenges of human health improvement. Bioprocess development, or biomanufacturing, is an important step in anti-cancer therapy developments. Novel surface receptors were revealed by integrating proteomics data and live-cell characterization, and were used for antibody design with improved specific targeting. A high titer (>2 g/L) of monoclonal antibody (mAb) was produced by Chinese hamster ovary cells from fed-batch cell culture. Live-cell confocal microscopy imaging and flow cytometry analysis demonstrated the strong and specific binding of the produced mAb to cancer cell lines. The cancer treatment effect of mAb was enhanced through the antibody-drug conjugate (ADC) technology. Various conjugation conditions of mAb and drug, including linker selection, ratio of drug and mAb, and conjugation approaches, were investigated to improve the production yield and product quality. High quality human T cell biomanufacturing was investigated to accelerate the cancer cellular therapy development in the next stage. More than 1 billion human T cells were expanded through a 4 day long culture. T cell quality was confirmed by 15 markers using flow cytometry. Finally, an Omics-based mathematical model was established to guide the rational design for process development. A biofuel substitute with high economic value, biobutanol, was used as a model chemical. The model integrated the proteomics, metabolomics, and production kinetics. Rational design strategies were then proposed and confirmed. In-depth understanding of bioprocess from this study will benefit the novel anti-cancer therapies development in the future.

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Engineering Commons

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