Gaining ground on a cure through synergy: combining checkpoint inhibitors with cancer vaccines

Expert Rev Clin Immunol. 2016 Dec;12(12):1347-1357. doi: 10.1080/1744666X.2016.1202114. Epub 2016 Jun 28.

Abstract

The approval of multiple checkpoint inhibitors (CPIs) for the treatment of advanced malignancies has sparked an explosion of research in the field of cancer immunotherapy. Despite the success of these medications, a large number of patients with advanced malignancy do not benefit from therapy. Early research indicates that a therapeutic combination of cancer vaccines with checkpoint inhibitors may lead to synergistic effects and higher response rates than monotherapy. Areas covered: This paper summarizes the previously completed and ongoing research on this exciting combination, including the use of the tumor lysate, particle-loaded dendritic cell (TLPLDC) vaccine combined with checkpoint inhibitors in advanced melanoma. Expert commentary: Increasing experience with CPIs has led to improved understanding of which patients may benefit and it is increasingly clear that the presence of a pre-existing immune response to the tumor, along with tumor-infiltrating lymphocytes, is key to the success of CPIs. One exciting possibility for the future is the addition of a cancer vaccine to CPI therapy, eliciting these crucial T cells, which can then be augmented and protected by the CPI. A number of current and future studies are addressing this very exciting combination therapy.

Keywords: CTLA-4; Checkpoint inhibitor; PD-1; PD-L1; TLPLDC vaccine; cancer immunotherapy; cancer vaccine; melanoma; tumor microenvironment; tumor-infiltrating lymphocytes.

Publication types

  • Review

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cell Cycle Checkpoints / drug effects
  • Combined Modality Therapy
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Growth Inhibitors / therapeutic use*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Melanoma / immunology
  • Melanoma / therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*
  • Tumor Microenvironment

Substances

  • Cancer Vaccines
  • Growth Inhibitors