T cells as vehicles for cancer vaccination

Abstract

The success of cancer vaccines is dependent on the delivery of tumor-associated antigens (TAAs) within lymphoid tissue in the context of costimulatory molecules and immune stimulatory cytokines. Dendritic cells (DCs) are commonly utilized to elicit antitumor immune responses due to their attractive costimulatory molecule and cytokine expression profile. However, the efficacy of DC-based vaccines is limited by the poor viability and lymph-node migration of exogenously generated DCs in vivo. Alternatively, adoptively transferred T cells persist for long periods of time in vivo and readily migrate between the lymphoid and vascular compartments. In addition, T cells may be genetically modified to express both TAA and DC-activating molecules, suggesting that T cells may be ideal candidates to serve as cellular vehicles for antigen delivery to lymph node-resident DCs in vivo. This paper discusses the concept of using T cells to induce tumor-specific immunity for vaccination against cancer.

Figure 1

Targeting dendritic cells (DCs) in vivo using T cells for cancer vaccination. Upon infusion, T cells efficiently home to lymphoid tissue where they encounter lymph node-resident DCs. T cells may be genetically modified to express tumor-associated antigens as well as molecules that can induce DC activation, such as CD40L, heat shock proteins (HSPs), and flagellin. Interacting DCs engulf and present antigen delivered by T cells on MHC class I and II molecules. T cell-mediated DC maturation results in the upregulation of costimulatory molecules, such as CD80 and CD86, which are necessary for the generation of potent helper CD4⁺ and effector CD8⁺ T cell responses.