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Cancer vaccines based on dendritic cells loaded with tumor-associated antigens

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Abstract

Dendritic cells (DCs) can be used as an antigen presentation platform for vaccination against cancer. In this approach, DCs are expanded in vitro from monocyte-derived progenitors, and subsequently loaded with well-characterized tumor-associated antigens (TAAs). TAAs can be incubated with DCs in various forms, including peptides, recombinant proteins, plasmid DNA, formulated RNA, or recombinant viruses. Advantages and limitations of DC-based cellular vaccines against cancers, as well as preliminary results of clinical studies already performed in humans, are discussed. Importantly, significant advances in our understanding of the biology of DCs can be used to support the design of new vaccines or adjuvants in order to elicit TH1 cellular immune responses.

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References

  • Almand B, Reser JR, Lindman B, et al. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res. 2000;6:1755–66.

    PubMed  CAS  Google Scholar 

  • Avigan D. Dendritic cells: development, function and potential use for cancer immunotherapy. Blood Rev. 1999;13:51–64.

    Article  PubMed  CAS  Google Scholar 

  • Banchereau J, Steinman R. Dendritic cells and the control of immunity. Nature. 1998;392:245–52.

    Article  PubMed  CAS  Google Scholar 

  • Boczkowski D, Nair SK, Nam J-H, Lyerly HK, Gilboa E. Induction of tumor immunity and cytotoxic T lymphocyte responses using dendritic cells transfected with messenger RNA amplified from tumor cells. Cancer Res. 2000;60:1028–34.

    PubMed  CAS  Google Scholar 

  • Bonnet MC, Tartaglia J, Verdier F, et al. Recombinant viruses as a tool for therapeutic vaccination against human cancers. Immunol Lett. 2000;74:11–25.

    Article  PubMed  CAS  Google Scholar 

  • Burch PA, Breen JK, Buckner JC, et al. Priming tissue-specific cellular immunity in a phase I trial of autologous dendritic cells for prostate cancer. Cancer Res. 2000;6:2175–82.

    CAS  Google Scholar 

  • Carbone FR, Kurts C, Bennett SR, Miller JF, Heath WR. Cross-presentation: a general mechanism for CTL immunity and tolerance. Immunol Today. 1998;19:368–73.

    Article  PubMed  CAS  Google Scholar 

  • Cella M, Sallusto F, Lanzavecchia A. Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol. 1997;9:10–16.

    Article  PubMed  CAS  Google Scholar 

  • Charbonnier A, Gaugler B, Sainty D, Lafage-Pochitaloff M, Olive D. Human acute myeloblastic leukemia cells differentiate in vitro into mature dendritic cells and induce the differentiation of cytotoxic T cells against autologous leukemias. Eur J Immunol. 1999;29:2567–78

    Article  PubMed  CAS  Google Scholar 

  • Chaux P, Luiten R, Demotte N, et al. Identification of five mage-A1 epitopes recognized by cytolytic T lymphocytes obtained by in vitro stimulation with dendritic cells transduced with MAGE-A1. J Immunol. 1999;22:1767–99.

    Google Scholar 

  • Cho BK, Palliser D, Guillen E, et al. A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins. Immunity. 2000;12:263–72.

    Article  PubMed  CAS  Google Scholar 

  • Dallal RM, Lotze MT. The dendritic cell and human cancer vaccines. Curr Opin Immunol. 2000;12:583–8.

    Article  PubMed  CAS  Google Scholar 

  • Drakesmith H, Chain B, Beverley P. How can dendritic cells cause autoimmune disease? Immunol Today. 2000;21:214–17.

    Article  PubMed  CAS  Google Scholar 

  • Fong L. Dendritic cells in cancer immunotherapy. Annu Rev Immunol. 2000;18:254–73.

    Article  Google Scholar 

  • Gabrilovich DI, Chen HL, Girgis KR, et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nature Med. 1996;2:1096–102.

    Article  PubMed  CAS  Google Scholar 

  • Gabrilovich DI, Corak J, Ciernik IF, Kavanaugh D, Carbone DP. Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res. 1997;3:483–90.

    PubMed  CAS  Google Scholar 

  • Gong J, Avigan D, Chen D, et al. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc Natl Acad Sci USA. 2000a;97:2715–18.

    Article  PubMed  CAS  Google Scholar 

  • Gong J, Nikrui N, Chen D, et al. Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol. 2000b;165:1705–11.

    PubMed  CAS  Google Scholar 

  • Grabbe S, Kämpgen E, Schuler G. Dendritic cells: multi-lineal and multi-functional. Immunol Today. 2000;21:431–3.

    Article  PubMed  CAS  Google Scholar 

  • Henderson RA, Nimgaonkar MT, Watkins SC, Robbins PD, Ball ED, Finn OJ. Human dendritic cells genetically engineered to express high levels of the human epithelial tumor antigen mucin (MUC-1). Cancer Res. 1996;56: 3763–70.

    PubMed  CAS  Google Scholar 

  • Hsu FJ, Benike C, Fagnoni F, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nature Med. 1996;2:52–8.

    Article  PubMed  CAS  Google Scholar 

  • Kalinski P, Hilkens CM, Wierenga EA, Kapsenberg ML. T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol Today. 1999;20:561–7.

    Article  PubMed  CAS  Google Scholar 

  • Kawashima I, Tsai V, Southwood S, Takesako K, Sette A, Celis E. Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res. 1999;59:431–5.

    PubMed  CAS  Google Scholar 

  • Kim CJ, Prevette T, Cornier J, et al. Dendritic cells infected with poxviruses encoding MART-1/Melan A sensitize T lymphocytes in vitro. J Immunol. 1997;20:276–86.

    CAS  Google Scholar 

  • Klein C, Bueler H, Mulligan RC. Comparative analysis of genetically modified dendritic cells and tumor cells as therapeutic cancer vaccines. J Exp Med. 2000;191:1699–708.

    Article  PubMed  CAS  Google Scholar 

  • Kugler A, Stuhler G, Walden P, et al. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nature Med. 2000;6:332–6.

    Article  PubMed  CAS  Google Scholar 

  • Lanzavecchia A, Sallusto F. Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells. Science. 2000;290:92–7.

    Article  PubMed  CAS  Google Scholar 

  • Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML. Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a phase II clinical trial. Cancer Res. 2000;60:829–33.

    PubMed  CAS  Google Scholar 

  • Ludewig B, Ochsenbein AF, Odermat B, Paulin D, Hengartner H, Zinkernagel RM. Immunotherapy with dendritic cells directed against tumor antigens shared with normal host cells results in severe autoimmune disease. J Exp Med. 2000;191:795–803.

    Article  PubMed  CAS  Google Scholar 

  • Lynch DH, Andreasen A, Maraskovsky E, Whitmore J, Miller RE, Schuh JC. Flt3 ligand induces tumor regression and antitumor immune responses in vivo. Nature Med. 1997;3:625–31.

    Article  PubMed  CAS  Google Scholar 

  • McLellan AD, Kampgen E. Functions of myeloid and lymphoid dendritic cells. Annu Rev Immunol. 2000;18:767–811.

    Article  Google Scholar 

  • Melero I, Vile RG, Colombo MP. Feeding dendritic cells with tumor antigens: self-service buffet or a la carte? Gene Ther. 2000;7:1167–70.

    Article  PubMed  CAS  Google Scholar 

  • Moingeon P. Cancer vaccines. Vaccine. 2001;19:1305–26.

    Article  PubMed  CAS  Google Scholar 

  • Morse MA, Deng Y, Coleman D, et al. A phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen. Clin Cancer Res. 1999;5:1331–8.

    PubMed  CAS  Google Scholar 

  • Murphy G., Tjoa B., Ragde H., Kenny G., Boynton A. Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrame antigen. Prostate. 1996;29:371–80.

    Article  PubMed  CAS  Google Scholar 

  • Nestlé FO, Alijagic S, Gilliet M, et al. Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells. Nature Med. 1998;4:328–32.

    Article  PubMed  Google Scholar 

  • Norbury CC, Chambers BJ, Prescott AR, Ljunggren HG, Watts C. Constitutive macropinocytosis allows TAP-dependent major histocompatibility complex class I presentation of exogenous soluble antigen by bone marrow-derived dendritic cells. Eur J Immunol 1997;27:280–8.

    PubMed  CAS  Google Scholar 

  • Offrienga R, van der Burg S, Ossendorp F, Toes RE, Melief CJ. Design and evaluation of antigen-specific vaccination strategies against cancer. Curr Opin Immunol. 2000;2:576–82.

    Article  Google Scholar 

  • Pettit AR, Thomas R. Dendritic cells: the driving force behind autoimmunity in rheumatoid arthritis? Immunol Cell Biol. 1999;77:420–7.

    Article  PubMed  CAS  Google Scholar 

  • Pierre P, Mellman I. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Cell. 1998;93:1135–45.

    Article  PubMed  CAS  Google Scholar 

  • Rea D, van Kooten C, van Meijgaarden KE, Ottenhoff TH, Melief CJ, Offrienga R. Glucocorticoids transform CD-40-triggering of dendritic cells into an alternative activation pathway resulting in antigen-presenting cells that secrete IL-10. Blood. 2000;95:3162–7.

    PubMed  CAS  Google Scholar 

  • Reid SD, Penna G, Adorini L. The control of T cell responses by dendritic cell subsets. Curr Opin Immunol. 2000;12:114–21.

    Article  PubMed  CAS  Google Scholar 

  • Russo V, Tanzarella S, Dalerba P, et al. Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response. Proc Natl Acad Sci USA. 2000;97:2185–90.

    Article  PubMed  CAS  Google Scholar 

  • Sallusto F, Lanzavecchia A. Mobilizing dendritic cells for tolerance, priming, and chronic inflammation. J Exp Med. 1999;189:611–14.

    Article  PubMed  CAS  Google Scholar 

  • Shimizu K, Fields RC, Giedlin M, Mule JJ. Systemic administration of interleukin 2 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines. Proc Natl Acad Sci USA. 1999;96:2268–73.

    Article  PubMed  CAS  Google Scholar 

  • Singh-Jasuja H, Toes RE, Spee P, et al. Cross-presentation of glycoprotein 96-associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis. J Exp Med. 2000;191:1965–74.

    Article  PubMed  CAS  Google Scholar 

  • Slingluff CL, Hunt D, Engelhard VH. Direct analysis of tumor-associated peptide antigens. Curr Opin Immunol. 1994;6:733–40.

    Article  PubMed  CAS  Google Scholar 

  • Smith CA, Woodruff LS, Kitchingman GR, Rooney CM. Adenovirus-pulsed dendritic cells stimulate human virus-specific T-cell responses in vitro. Virology. 1996;60:6733–40.

    Google Scholar 

  • Steinman RM, Pack M, Inaba K. Dendritic cell development and maturation. Adv Exp Med Biol. 1997;417:1–6.

    PubMed  CAS  Google Scholar 

  • Thurner B, Haendle I, Röder C, et al. Vaccination with Mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med. 1999;190:1669–78.

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Saffold S, Cao X, Krauss J, Chen W. Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol. 1998;161:5516–24.

    PubMed  CAS  Google Scholar 

  • Yang S, Kittlesen D, Slingluff CL Jr, Vervaert CE, Seigler HF, Darrow TL. Dendritic cells infected with a vaccinia vector carrying the human gp100 gene simultaneously present multiple specificities and elicit high-affinity T cells reactive to multiple epitopes and restricted by HLA-A2 and-A3. J Immunol. 2000;22:1767–00.

    Google Scholar 

  • Zitvogel L, Regnault A, Lozier A, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nature Med. 1998;4:594–600.

    Article  PubMed  CAS  Google Scholar 

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Burdin, N., Moingeon, P. Cancer vaccines based on dendritic cells loaded with tumor-associated antigens. Cell Biol Toxicol 17, 67–75 (2001). https://doi.org/10.1023/A:1010944003649

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