Training in Pediatric Cancer Research: Targeting Tim-3

Background

Therapeutic vaccines for cancer would benefit from approaches that direct immune cell populations toward specific functions. Polymer vaccine depots loaded with neuroblastoma antigens are in development. These depots can be deposited in lymph nodes to slowly release antigens and immune modulators to direct the differentiation CD8+ T cells. Additionally, recent studies reveal that Tim-3 pathway play an active role in restraining anti-tumor T cell immunity. This project will test if RNA-based knock-down of Tim-3 enhances cancer vaccination in mouse models of neuroblastoma.

Project Goal

The first phase will focus on loading depots with Tim-3 shRNA. I will then characterize the loading of each component and use a primary dendritic cell/T cell co-culture system to assess Tim-3 knockdown and increased activation of T cells. In the second phase, these depots will be used to immunize mice on Day 0 (prophylactic) or Day 10 (therapeutic) with respect to N2a tumor challenge. Tumor burden will then be monitored over time, along with T cell specificity (tested by antigen restimulation) and Tim-3 expression (tested by antibody staining).