Dendritic Cells in Cancer Immunotherapy: Vaccines, Live Adjuvants and DC-assisted T Cell Therapies

Clinical effectiveness of immune therapies of solid tumors requires a) the induction or expansion of T cells able of recognizing multiple variants of cancer cells present in each cancer patient, and b) the ability of tumor-specific cytotoxic T cells (CTLs) and other effector cells to enter all sites of the tumor, which typically display significant heterogeneity of the tumor microenvironment (TME). For this reason, “cold” tumors, which lack CTL infiltration are uniformly nonresponsive to immune therapies and are less responsive to chemo- and radiotherapy, which also mobilize secondary immune phenomena.

Our group has developed four groups of strategies to enhance uniform targeting of the antigenically heterogenous cancer cells and to eliminate the “cold” tumor phenotypes:  1) Cell-based immunotherapies with dendritic cells (DC), used as antigen-loaded live vaccines or intratumorally injected live adjuvants; 2)  DC-induced multi-epitope-specific CTLs; 3) Dual-targeting T cells recognizing tumor-associated antigens (TAAs) and cancer-expressed NKR ligands; and 4) Combinatorial adjuvants which selectively enhance tumor influx of CTLs (but not Tregs). Preclinical data and results of recent clinical trials will be presented.

Learning Objectives: 

1. Identify the key roles of dendritic cells in cancer immunotherapy, including their use as antigen-loaded vaccines and intratumoral adjuvants.

2. Explain the strategies used to overcome tumor heterogeneity and “cold” tumor phenotypes, with a focus on enhancing cytotoxic T cell infiltration and activity.

3. Evaluate the therapeutic potential of DC-assisted T cell therapies and combinatorial adjuvants based on recent preclinical and clinical trial findings.