Dendritic cell-based cancer immunotherapies
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Because of their unique role in linking the innate and adaptive immune systems, dendritic cells (DCs) have been a logical focus for novel immunotherapies. However, strategies employing active immunization with ex vivo generated and antigen–pulsed DCs have shown limited efficacy in clinical trials. These past approaches did not take into account the complex interactions between cells of the innate immune system and DCs during DC maturation, antigen processing, and presentation to naïve T cells. By better understanding the natural sequence of events occurring in vivo during an effective immune response, we can tailor antitumor immunotherapeutic strategies to augment aspects of this response from the activation of innate immune cells to antigen uptake and DC maturation to priming of naïve T cells and, ultimately, to the establishment of antitumor immunity. Current DC vaccination strategies utilize a number of methods to recapitulate the cascade of events that culminate in a protective antitumor immune response.
Keywordsdendritic cells (DCs) adjuvant ex vivo DC therapy in vivo DC therapy immunotherapy
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- Bezbradica JS, Stanic AK, Matsuki N et al (2005) Distinct roles of dendritic cells and B cells in Vα14Jα18 natural T cell activation in vivo. J Immunol 174:4 696–705Google Scholar
- Fujii S, Fujimoto K, Shimizu K et al (1999) Presentation of tumor antigens by phagocytic dendritic cell clusters generated from human CD34+ hematopoietic progenitor cells: induction of autologous cytotoxic T lymphocytes against leukemic cells in acute myelogenous leukemia patients. Cancer Res 59: 2150–2158PubMedGoogle Scholar
- Manegold C, Gravenor D, Woytowitz D et al (2008) Randomized phase II trial of a Toll-like receptor 9 agonist oligodeoxynucleotide, PF-3512676, in combination with first-line taxane plus platinum chemotherapy for advanced-stage non-small-cell lung cancer. J Clin Oncol 26: 3979–3986PubMedCrossRefGoogle Scholar
- Sauter B, Albert ML, Francisco L et al (2000) Consequences of cell death. Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191: 423–434Google Scholar
- Soiffer R, Lynch T, Mihm M et al (1998) Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 95: 13141–13146PubMedCrossRefGoogle Scholar
- Solinger AM, Ultee ME, Margoliash E et al (1979) T-lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two complementing major histocompatibility complex-linked immune response genes. J Exp Med 150: 830–848PubMedCrossRefGoogle Scholar
- Stuge TB, Holmes SP, Saharan S et al (2004) Diversity and recognition efficiency of T cell responses to cancer. PLoS Med 1: e28 Su Z, Dannull J, Yang BK et al–2005 Telomerase mRNA transfected dendritic cells stimulate antigenspecific CD8 and CD4 T cell responses in patients with metastatic prostate cancer J Immunol 17437983807CrossRefGoogle Scholar
- Wood C, Srivastava P, Bukowski R et al (2008) An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicenter, open-label, randomised phase III trial. Lancet 372: 145–154PubMedCrossRefGoogle Scholar