Enhancing cancer immunotherapy by intracellular delivery of cell-penetrating peptides and stimulation of pattern-recognition receptor signaling

Adv Immunol. 2012:114:151-76. doi: 10.1016/B978-0-12-396548-6.00006-8.

Abstract

The importance of T-cell-mediated antitumor immunity has been demonstrated in both animal models and human cancer immunotherapy. In the past 30 years, T-cell-based immunotherapy has been improved with an objective clinical response rate of up to 72%. Identification of MHC class I- and II-restricted tumor antigens recognized by tumor-reactive T cells has generated a resurgence of interest in cancer vaccines. Although clinical trials with cancer peptide/protein vaccines have only met a limited success, several phase II/III clinical trials are either completed or ongoing with encouraging results. Recent advances in immunotherapy have led to the approval of two anticancer drugs (sipuleucel-T vaccine and anti-CTLA-4 antibody) by the US FDA for the treatment of metastatic castration-resistant prostate cancer and melanoma, respectively. Intracellular delivery of antigenic peptides into dendritic cells (DCs) prolongs antigen presentation of antigen-presenting cells to T cells, thus further improving clinical efficacy of peptide/protein cancer vaccines. Because innate immune responses are critically important to provide sensing and initiating of adaptive immunity, combined use of cell-penetrating peptide vaccines with stimulation of innate immune signaling may produce potent antitumor immune responses. We will discuss the recent progress and novel strategies in cancer immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use*
  • Cell-Penetrating Peptides / immunology*
  • Cytokine-Induced Killer Cells / immunology
  • Dendritic Cells / immunology
  • Humans
  • Immunotherapy / methods
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Receptors, Pattern Recognition / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / immunology

Substances

  • Cancer Vaccines
  • Cell-Penetrating Peptides
  • Receptors, Pattern Recognition
  • Vaccines, Subunit
  • Vaccines, Synthetic