Cancer immunotherapy: In vivo imaging of adoptively transferred T cells in an immunocompetent host

Abstract

The field of cancer immunotherapy has seen several recent successes as a result of an improved understanding of T-cell regulation and responses. The foundation for these successes existed in earlier work consisting of the identification of tumor antigens that could be recognized by cytotoxic T cells with the eventual elimination of tumor cells (1, 2). On the basis of these early studies, initial clinical trials focused on antigen-specific methods (e.g., peptide, protein, and DNA vaccines) to expand T cells in an attempt to generate antitumor responses. Unfortunately, many of these vaccine trials failed to demonstrate clinical efficacy (3). Investigations as to why these initial trials failed led to the identification of a complex system that includes intrinsic mechanisms that control T-cell responses [cytotoxic lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1)], extrinsic mechanisms that control T-cell responses (regulatory T cells), cytokine pathways that act to regulate T-cell responses [granulocyte macrophage colony-stimulating factor (GM-CSF), TGF-β], and lack of sufficient quantities of T cells with high-affinity T-cell receptors against tumor antigens. Immunotherapy strategies are now addressing these complex …