Immune Targeted Shortwave Infrared Emitting Nanoprobes For The Prognostication Of Cancer

Jake N. Siebert
Biomedical Engineering PhD Dissertation Defense 

Abstract: Despite significant advances in detection and treatment metastatic triple negative breast cancer remains a largely incurable disease, stressing the importance of novel methods for prognosticating disease course to better stratify patients and identify early metastases. It has become increasingly clear that the immune system plays a critical role in the development of the pre-metastatic niche, specifically the immunosuppressive myeloid-derived suppressor cell (MDSC) has been identified as a key factor in niche formation. This cell type has further been identified as a contributor to immune evasion and immunotherapy resistance within the primary tumor. For this reason, interest has grown in the use of MDSCs as a potential biomarker for cancer prognostication.

This thesis is focused on the design of molecularly targeted optical nanoprobes for the tracking of MDSCs in vivo for the prognostication and monitoring of breast cancer progression. This work demonstrates that shortwave infrared (SWIR) emitting nanoprobes can be engineered for the targeting of MDSCs, permitting the visualization of the lung pre-metastatic niche in a murine model of breast cancer, and distinguish between two models with differing metastatic propensities. Furthermore, it builds on this work by exploring the capabilities of immune SWIR imaging for monitoring immune dynamics in response to immune checkpoint inhibitor therapy in the primary tumor using both CD8+ T cell- and MDSC-targeted nanoprobes. Overall this thesis demonstrates the potential of SWIR-emitting probes for MDSC tracking and cancer prognostication.

Advisor: 
Prabhas Moghe, PhD

Committee Members:
Vidya Ganapathy, PhD
Charles Roth, PhD
Edmund Lattime, PhD

Location: BME 122 or via Zoom https://rutgers.zoom.us/j/96521580701?pwd=R2uaRUX238IYtjWUzAcnMnfJneN96o.1&from=addon#success