Leveraging Biomaterials to Direct Immune Function in Cancer and Autoimmunity

Abstract

Immune dysregulation and difficulties in directing immune function in cancer and autoimmune disease pose complex challenges for existing vaccines and immunotherapies. In cancer, tumor cells exploit processes to evade the immune system. Conversely, autoimmune diseases such as multiple sclerosis (MS) occur when immune cells incorrectly attack healthy host tissue and cells. To address the dichotomy of dysregulated immune responses that can arise, next generation vaccines and immunotherapies demand better control over the specificity and types of immune of responses generated within lymph nodes (LNs).

This dissertation investigated two approaches to improve immune signal delivery for precision control over immune responses. In the first approach, self-assembling vaccine nanoparticles were engineered with tunable charge and cargo loading to efficiently deliver immune signals in specific combinations and doses without compromising function. These studies offer new insight into biomaterial design for therapeutic cancer vaccines and demonstrate that the physiochemical properties of biomaterials - particularly the interplay between charge, uptake, and affinity - play an important role in the immune signals that can promote T cell expansion against tumor antigens.

In the second approach, a biomaterial-based platform is used to control immune signal delivery to LNs during autoimmunity. Direct injections of therapeutic vaccine carriers into the LNs of mice offer new insight into how the localized combination of myelin peptide (MOG) and rapamycin (Rapa) - an immunomodulatory signal, promote potent and selective immune tolerance. This body of work demonstrates that immune function is highly localized to the signals delivered to the LNs, requiring an idealized combination of both self-antigen and immunomodulatory signal to promote the proliferation, retention, and polarization of antigen specific T cells towards regulatory T cells that can selectively limit inflammatory T cell phenotypes and combat autoimmunity.

Together, these two approaches offer new insight into how biomaterials can be rationally harnessed to direct immune function across cancer and autoimmune disease.