Dissertation Defense: Jenna Dombroski, Biomedical Engineering
DISSERTATION DEFENSE
Jenna Dombroski, Biomedical Engineering
*under the direction of Mike King
“Nano-vaccines and dendritic cell processing for anti-cancer therapies”
05.18.23 | 12:00PM CST | 5326 Stevenson Center | Zoom
1 in 8 women are diagnosed with breast cancer in her lifetime, representing a need for effective preventative measures and therapeutics. Dendritic cells (DCs) can be useful for effective anti-cancer vaccines. In this project, I have developed vaccines that activate DCs to initiate an immune response with the goal to improve current therapies.
A vaccine was fabricated comprised of cancer cell fragments and coined the term “tumor nano-lysate” (TNL). The resulting formulation was characterized by size, polydispersity index, protein contents and morphology. An in vivo study demonstrated the effectiveness of TNL at reducing tumor size, delaying metastasis onset, and increasing survival in the 4T1 orthotopic breast cancer model. This study aimed to determine the immune response elicited by the TNL vaccine, to enable future improvements to the formulation. Various immune cells and in particular, DCs, were activated by TNL, with changes in morphology, metabolism and cytokine release observed for DCs. The response to TNL was comparable to other stimulators, and in some cases, greater. An in vivo analysis determined that significant immunological responses were occurred within 3 days and that activation was reduced at 10 days. Following this study, a multi-dose in vivo study showed a trend in reduced tumor volume, increased survival, and delayed metastasis.
In a complementary project, DCs were used to develop an anti-cancer therapeutic vaccine. It was hypothesized that the mechanical forces of fluid shear stress (FSS) would cause the opening of mechanosensitive ion channels (MSCs) and a subsequent influx of calcium, thus activating DCs ex vivo. FSS was applied to DCs via a cone-and-plate device and compared to control conditions without force. DCs experienced changes in metabolism, morphology, and cytokine release following FSS. Activation was also observed in primary mouse and human cells, and similar trends were observed when applied to DCs isolated from cancer patient blood. FSS activation of DCs is easily scalable and could be used alone or in combination with current therapeutics to boost their efficacy and enhance T cell priming. With these therapeutic advances, it may be possible to reduce tumor burden and potentially increase life expectancy of metastatic cancer patients.