Brian Zou
Program: Unspecified
Current advisor:
Undergraduate university: Macalester College
Research summary
Toll-like Receptor 4(TLR4) is a well characterized receptor that enables Dendritic Cells (DCs) to distinguish between infected and normal cells that can be leveraged to effectively clear tumors, especially in cancers that have become immune tolerant. TLR4 uniquely signals through both MyD88 and TRIF pathways. Preliminary work in the DeSelm Lab successfully generated an engineered Dendritic Cell (αB7-TLR4 CAR-DC) that expresses a chimeric antigen receptor (CAR) specific to surface B7H3 tumor antigen, fused to the intracellular signaling domain of TLR4. Data shows αB7-TLR4 CAR-DCs effectively capture intracellular tumor-derived antigens like AF488-ova. However, the distinct roles of MyD88 and TRIF signaling pathways in these CAR DCs remain unclear. Thus, we proposed a project that generated CAR-DCs that had genetic homozygous knockouts of either MyD88 or TRIF to better characterize the impacts of these proteins on CAR-DC performance, both in vitro cross-priming assays and in vivo heterogenous B7H3 cancer expressing mice.
Graduate publications