Project 1: Transport of Effector T cells and Nano-DC vaccine in Breast Cancer

Co-Leader: Elizabeth A. Mittendorf, M.D., Ph.D.
Co-Leader: Rongfu Wang, Ph.D.
Co-Leader: Haifa Shen, M.D., Ph.D.

Dendritic cells (DCs) are professional antigen-presenting cells that can process and present tumor antigen to T cells to initiate immune responses. Therefore, DC vaccines are a logical choice for therapeutic intervention. In order for a DC vaccine to elicit the proper immune responses, a sequence of physical and biological events must occur:

  1. the DC vaccine must migrate from the injection site to lymphoid tissues;
  2. the DC vaccine must maintain a mature stimulatory status to persistently process and present the immunizing antigen to T cells; and
  3. the antigen-specific T cells must travel to the tumor-bearing organ and infiltrate into the tumor microenvironment to exert their antitumor activity. These events are often insurmountable hurdles for most DC vaccines.

Clinical studies have shown that less than 5% of intradermally injected DCs can reach the lymph nodes. The stimulatory signals of ex vivo-matured DCs cannot be maintained in vivo. Furthermore, the tumor microenvironment prevents infiltration of the cytotoxic T cells. Overcoming these sequential barriers is critical for developing an effective DC vaccine. Accumulation of DC vaccines in the lymph nodes, especially tumor-draining lymph nodes, may depend on successful negotiation of the sequential physical and biological barriers. In addition, modification of the tumor microenvironment will potentially facilitate transport of effector T cells and drugs, which combined with our Nano-DC vaccine, would significantly improve cancer therapy.

Project 1  |  Project 2  |  Transport Oncophysics Core