Epitope-based vaccines that induce CD8-positive T-cell responses to tumor-associated antigens are being investigated in the treatment of several types of cancer. In a study reported in Clinical Cancer Research, Nagato and colleagues showed that combined immunotherapy with polyinosinic-polycytidylic acid (poly-IC) and anti–programmed death-ligand 1 (PD-L1) monoclonal antibody produced dramatic reduction in tumor growth in mouse models of tumors with no identified tumor-associated antigens.
Combined treatment with poly-IC and anti-PD-L1 monoclonal antibody was assessed in mouse models of melanoma, lung cancer, and colon cancer. Treatment was associated with potent immune responses resulting in eradication or dramatic reduction of tumor growth, with enduring protection against tumor rechallenge being observed in some cases.
The findings indicated that the activity of immunotherapy was mediated by CD8-positive T cells but not CD4-positive T cells or natural killer NK cells. Studies in genetically deficient mice showed that the efficacy of poly-IC and anti-PD-L1 monoclonal antibody therapy was dependent on activity of type I interferons, with interferon-gamma not appearing to play a central role.
The investigators concluded, “The overall results suggest that immunotherapy consisting of the combination of poly-IC/anti-PD-L1 [monoclonal antibody] could be a promising new approach for treating cancer patients, especially those instances where no reliable [tumor-associated antigens] are available as a therapeutic vaccine.” ■
Nagato T, et al: Clin Cancer Res. January 3, 2014 (early release online).
