title: Enhancing cancer immunotherapy by intracellular delivery of cell-penetrating peptides and stimulation of pattern-recognition receptor signaling.
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.
authors.affiliation: Department of Pathology and Immunology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D057846:Cell-Penetrating Peptides / Q000276:immunology*; D055612:Cytokine-Induced Killer Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D057846:Cell-Penetrating Peptides; D051192:Receptors, Pattern Recognition; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic