Cancer immunotherapy has been attempted for more than a century, and investment has intensified in the last 20. years. The complexity of the immune system is exemplified by the myriad of immunotherapeutic approaches under investigation. While anti-tumor immunity has been achieved experimentally with multiple effector cells and molecules, particular promise is shown for harnessing the CD8 T cell response. Tumor cell-based vaccines have been employed in hundreds of clinical trials to date and offer several advantages over subunit and peptide vaccines. However, tumor cell-based vaccines, often aimed at cross priming tumor-reactive CD8 T cells, have shown modest success in clinical trials. Here we review the mechanisms of cross priming and discuss strategies to increase the efficacy of tumor cell-based vaccines. A synthesis of recent findings on tissue culture conditions, cell death, and dendritic cell activation reveals promising new avenues for clinical investigation.
Bibliographical noteFunding Information:
We thank the following funding support mechanisms: (B.M.A.) NIH Medical Scientist Training Program Grant T32 GM008244, Torske Klubben Fellowship for Minnesota Residents, and the Cancer Biology Training Grant T32 CA009138—36; and R01 CA154345, R01 CA160782, the American Cancer Society grant RSG-09-189-01-LIB, generous support from the Minnesota Medical Foundation, the Hedberg Family Foundation, and the Children’s Cancer Research Fund to J.R.O.
- Dendritic cells