Engineered Materials for Improving Cancer Immunotherapy
Cheung, Alexander Sing
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AbstractImmunotherapy, the treatment of disease through targeted activation of the immune system, has recently shown unprecedented clinical success for diverse malignancies. In contrast to traditional cancer treatments, which are associated with widespread off-target toxicity and frequent disease recurrence, successful cancer immunotherapies promote an adaptive immune response that is both cancer-specific and highly durable. Nevertheless, many cancer immunotherapy approaches elicit suboptimal responses or are nonfunctional for a large patient population. Although there are many reasons for this that are tied to our incomplete understanding of the immune system, a key limitation common to many cancer immunotherapy approaches relates to the lack of spatiotemporal control with which immune-directing cues are presented to the immune system. Designing biomaterials to interface these cues with the immune system in a spatiotemporally controlled manner is a promising way to improve current cancer immunotherapies.
The general goal of this thesis was to develop materials to improve the spatiotemporal presentation of cues to the immune system as a means of eliciting a more robust response. Specifically, this thesis describes two approaches for improving distinct types of cancer immunotherapy: (1) a method for processing cancer cells that co-localizes native cancer antigens and adjuvants in particles that can be used for cancer vaccination, and (2) the use of an antigen-presenting cell-mimetic material that rapidly expands functional T cells for adoptive T cell transfer. We demonstrate that by designing these systems to present the respective immune-directing cues in a spatiotemporal pattern that mimics how the cues are naturally presented, a stronger response can be elicited from the immune system. Broadly, the results presented in this thesis illustrate the importance of presenting cues to the immune system in an appropriate spatiotemporal context, and show how biomaterials can be designed to facilitate this. Specifically, this thesis describes two potentially translatable systems that could be used to improve current approaches for therapeutic cancer vaccination and adoptive T cell transfer.
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