Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting

The realization that dendritic cells (DCs) orchestrate innate and adaptive immune responses has stimulated research on harnessing DCs to create more effective vaccines. Early clinical trials exploring autologous DCs that were loaded with antigens ex vivo to induce T-cell responses have provided proof of principle. Here, we discuss how direct targeting of antigens to DC surface receptors in vivo might replace laborious and expensive ex vivo culturing, and facilitate large-scale application of DC-based vaccination therapies.

[1]  G. Schuler,et al.  Rapid Induction of Tumor-specific Type 1 T Helper Cells in Metastatic Melanoma Patients by Vaccination with Mature, Cryopreserved, Peptide-loaded Monocyte-derived Dendritic Cells , 2002, The Journal of experimental medicine.

[2]  G. Belz,et al.  Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity , 2006, Nature Immunology.

[3]  J. Weber,et al.  Phase I Trial Of Intravenous Peptide-Pulsed Dendritic Cells in Patients With Metastatic Melanoma , 2001, Journal of immunotherapy.

[4]  M. Wright,et al.  Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN , 2006, International immunology.

[5]  J. Davoust,et al.  ER–phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells , 2003, Nature.

[6]  B. Barlogie,et al.  Protein transduction of dendritic cells for NY-ESO-1-based immunotherapy of myeloma. , 2005, Cancer research.

[7]  M. Blank,et al.  Regulated Expression of FcγR in Human Dendritic Cells Controls Cross-Presentation of Antigen-Antibody Complexes1 , 2006, The Journal of Immunology.

[8]  P. Albers,et al.  Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma. , 2003, Human gene therapy.

[9]  D. Underhill,et al.  Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. , 2005, Blood.

[10]  J. V. D. van de Winkel,et al.  Inefficient antigen presentation via the IgA Fc receptor (FcalphaRI) on dendritic cells. , 2006, Immunobiology.

[11]  Olivier Lantz,et al.  Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial , 2005, Journal of Translational Medicine.

[12]  P. Kloetzel Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII , 2004, Nature Immunology.

[13]  J. Connolly,et al.  A Novel Human Cancer Vaccine Elicits Cellular Responses to the Tumor-Associated Antigen, Human Chorionic Gonadotropin β , 2004, Clinical Cancer Research.

[14]  C. Figdor,et al.  Internalizing Antibodies to the C-Type Lectins, L-SIGN and DC-SIGN, Inhibit Viral Glycoprotein Binding and Deliver Antigen to Human Dendritic Cells for the Induction of T Cell Responses , 2006, The Journal of Immunology.

[15]  Y. Waeckerle‐Men,et al.  PLGA microspheres for improved antigen delivery to dendritic cells as cellular vaccines. , 2005, Advanced drug delivery reviews.

[16]  R. Germain,et al.  Major histocompatibility complex class I presentation of peptides derived from soluble exogenous antigen by a subset of cells engaged in phagocytosis , 1995, The Journal of experimental medicine.

[17]  C. Leclerc,et al.  Delivery of Multiple Epitopes by Recombinant Detoxified Adenylate Cyclase of Bordetella pertussisInduces Protective Antiviral Immunity , 2001, Journal of Virology.

[18]  A. Enk,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 , 1999, The Journal of experimental medicine.

[19]  Mark M. Davis,et al.  Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Bevan,et al.  Class I-restricted processing and presentation of exogenous cell- associated antigen in vivo , 1990, The Journal of experimental medicine.

[21]  R. Medzhitov,et al.  Toll-dependent selection of microbial antigens for presentation by dendritic cells , 2006, Nature.

[22]  E. Celis,et al.  Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen. , 1984, Science.

[23]  J. Connolly,et al.  Mannose Receptor Targeting of Tumor Antigen pmel17 to Human Dendritic Cells Directs Anti-Melanoma T Cell Responses via Multiple HLA Molecules , 2004, The Journal of Immunology.

[24]  R. Steinman,et al.  Activation of Natural Killer T Cells by -Galactosylceramide Rapidly Induces the Full Maturation of Dendritic Cells In Vivo and Thereby Acts as an Adjuvant for Combined CD4 and CD8 T Cell Immunity to a Coadministered Protein , 2003 .

[25]  T. Chang Regulation of immune response by antibodies: the importance of antibody and monocyte Fc receptor interaction in T-cell activation. , 1985, Immunology today.

[26]  T. Curiel,et al.  Tregs and rethinking cancer immunotherapy. , 2007, The Journal of clinical investigation.

[27]  I. Hakim,et al.  Enhanced major histocompatibility complex class I-dependent presentation of antigens modified with cationic and fusogenic peptides , 2000, Nature Biotechnology.

[28]  M. Wright,et al.  Molecular cloning of a C-type lectin superfamily protein differentially expressed by CD8alpha(-) splenic dendritic cells. , 2001, Molecular immunology.

[29]  Antonio Lanzavecchia,et al.  BDCA-2, a Novel Plasmacytoid Dendritic Cell–specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon α/β Induction , 2001, The Journal of experimental medicine.

[30]  R. Tampé,et al.  Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells , 2005, Nature Immunology.

[31]  S. Akira,et al.  A Subset of Toll-Like Receptor Ligands Induces Cross-presentation by Bone Marrow-Derived Dendritic Cells1 , 2003, The Journal of Immunology.

[32]  Ronald G. Crystal,et al.  Genetic medicines: treatment strategies for hereditary disorders , 2006, Nature Reviews Genetics.

[33]  E. Gilboa,et al.  Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. , 2002, The Journal of clinical investigation.

[34]  A. Goldberg,et al.  Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. , 1993, Nature.

[35]  E. Gilboa,et al.  Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. , 2005, The Journal of clinical investigation.

[36]  A. Mackensen,et al.  Phase I study in melanoma patients of a vaccine with peptide‐pulsed dendritic cells generated in vitro from CD34+ hematopoietic progenitor cells , 2000, International journal of cancer.

[37]  L. Chernomordik,et al.  Arginine-rich cell penetrating peptides: from endosomal uptake to nuclear delivery , 2005, Cellular and Molecular Life Sciences CMLS.

[38]  R. Steinman,et al.  The Dendritic Cell Receptor for Endocytosis, Dec-205, Can Recycle and Enhance Antigen Presentation via Major Histocompatibility Complex Class II–Positive Lysosomal Compartments , 2000, The Journal of cell biology.

[39]  H. Rammensee,et al.  Discrete Cleavage Motifs of Constitutive and Immunoproteasomes Revealed by Quantitative Analysis of Cleavage Products , 2001, The Journal of experimental medicine.

[40]  H. Ueno,et al.  Immune and Clinical Outcomes in Patients with Stage IV Melanoma Vaccinated with Peptide-Pulsed Dendritic Cells Derived From CD34+ Progenitors and Activated with Type I Interferon , 2005, Journal of immunotherapy.

[41]  V. Engelhard,et al.  Route of Immunization with Peptide-pulsed Dendritic Cells Controls the Distribution of Memory and Effector T Cells in Lymphoid Tissues and Determines the Pattern of Regional Tumor Control , 2003, The Journal of experimental medicine.

[42]  N. Kanazawa Dendritic cell immunoreceptors: C-type lectin receptors for pattern-recognition and signaling on antigen-presenting cells. , 2007, Journal of dermatological science.

[43]  R. Steinman,et al.  Tissue distribution of the DEC-205 protein that is detected by the monoclonal antibody NLDC-145. I. Expression on dendritic cells and other subsets of mouse leukocytes. , 1995, Cellular immunology.

[44]  Michel C. Nussenzweig,et al.  Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo , 2001, The Journal of experimental medicine.

[45]  G. Heller,et al.  Mature Human Langerhans Cells Derived from CD34+ Hematopoietic Progenitors Stimulate Greater Cytolytic T Lymphocyte Activity in the Absence of Bioactive IL-12p70, by Either Single Peptide Presentation or Cross-Priming, Than Do Dermal-Interstitial or Monocyte-Derived Dendritic Cells1 , 2004, The Journal of Immunology.

[46]  Sven Burgdorf,et al.  Distinct Pathways of Antigen Uptake and Intracellular Routing in CD4 and CD8 T Cell Activation , 2007, Science.

[47]  G. Bartsch,et al.  Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[48]  Hidde L. Ploegh,et al.  Analysis of Protease Activity in Live Antigen-presenting Cells Shows Regulation of the Phagosomal Proteolytic Contents During Dendritic Cell Activation , 2002, The Journal of experimental medicine.

[49]  L. Vitale,et al.  Antigenic Targeting of the Human Mannose Receptor Induces Tumor Immunity1 , 2007, The Journal of Immunology.

[50]  D. Valmori,et al.  Processing of tumor-associated antigen by the proteasomes of dendritic cells controls in vivo T-cell responses. , 2006, Cancer research.

[51]  S. Hue,et al.  Altered expression and endocytic function of CD205 in human dendritic cells, and detection of a CD205–DCL‐1 fusion protein upon dendritic cell maturation , 2007, Immunology.

[52]  G. Raposo,et al.  NOX2 Controls Phagosomal pH to Regulate Antigen Processing during Crosspresentation by Dendritic Cells , 2006, Cell.

[53]  D. Tough,et al.  Preferential Induction of CD4+ T Cell Responses through In Vivo Targeting of Antigen to Dendritic Cell-Associated C-Type Lectin-1 , 2006, The Journal of Immunology.

[54]  E. Gilboa,et al.  Induction of Tumor-Specific Cytotoxic T Lymphocytes in Cancer Patients by Autologous Tumor RNA-Transfected Dendritic Cells , 2002, Annals of surgery.

[55]  L. Zitvogel,et al.  Prospects for exosomes in immunotherapy of cancer , 2006, Journal of cellular and molecular medicine.

[56]  M. Bevan,et al.  Cd8+ but Not Cd8− Dendritic Cells Cross-Prime Cytotoxic T Cells in Vivo , 2000, The Journal of experimental medicine.

[57]  Gary Walsh,et al.  Biopharmaceutical benchmarks 2006 , 2006, Nature Biotechnology.

[58]  Masato Kato,et al.  Expression of human DEC-205 (CD205) multilectin receptor on leukocytes. , 2006, International immunology.

[59]  S. Gordon,et al.  Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. , 2005, Immunity.

[60]  Gary Walsh,et al.  Biopharmaceutical benchmarks , 2000, Nature Biotechnology.

[61]  M. Bevan,et al.  Presentation of exogenous protein antigens on major histocompatibility complex class I molecules by dendritic cells: pathway of presentation and regulation by cytokines. , 1997, Blood.

[62]  Dennis R. Burton,et al.  Human antibody–Fc receptor interactions illuminated by crystal structures , 2004, Nature Reviews Immunology.

[63]  R. Steinman,et al.  Differential Antigen Processing by Dendritic Cell Subsets in Vivo , 2007, Science.

[64]  K Mechtler,et al.  The influence of endosome-disruptive peptides on gene transfer using synthetic virus-like gene transfer systems. , 1994, The Journal of biological chemistry.

[65]  D. Ladant,et al.  In vivo induction of CTL responses by recombinant adenylate cyclase of Bordetella pertussis carrying viral CD8+ T cell epitopes. , 1996, Journal of immunology.

[66]  J. Ravetch,et al.  Fcgamma receptors: old friends and new family members. , 2006, Immunity.

[67]  C. Leclerc,et al.  In vivo induction of CTL responses by recombinant adenylate cyclase of Bordetella pertussis carrying multiple copies of a viral CD8(+) T-cell epitope. , 1999, FEMS immunology and medical microbiology.

[68]  T. Keler,et al.  Mannose receptor-targeted vaccines , 2004, Expert opinion on biological therapy.

[69]  P. Wallace,et al.  Toll-like receptor activation enhances cell-mediated immunity induced by an antibody vaccine targeting human dendritic cells , 2007, Journal of Translational Medicine.

[70]  A. Kaubisch,et al.  Enhanced antigen immunogenicity induced by bispecific antibodies , 1990, The Journal of experimental medicine.

[71]  Francesco Bertoni,et al.  Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1–polarizing program in dendritic cells , 2005, Nature Immunology.

[72]  E. Raz,et al.  Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism , 2000, Nature Biotechnology.

[73]  C. Figdor,et al.  Identification of DC-SIGN, a Novel Dendritic Cell–Specific ICAM-3 Receptor that Supports Primary Immune Responses , 2000, Cell.

[74]  I. Mellman,et al.  Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis , 2006, The Journal of experimental medicine.

[75]  S. Pöhlmann,et al.  Evidence that multiple defects in murine DC-SIGN inhibit a functional interaction with pathogens , 2005, Virology.

[76]  H. Klocker,et al.  Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells. , 1999, The Journal of urology.

[77]  D. Segal,et al.  Targeted antigen presentation using crosslinked antibody heteroaggregates. , 1987, Journal of immunology.

[78]  R. Steinman,et al.  Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. , 1999, The Journal of clinical investigation.

[79]  Michel C. Nussenzweig,et al.  Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance , 2002, The Journal of experimental medicine.

[80]  Kayo Nakamura,et al.  Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. , 2002, Immunity.

[81]  Henry C. Chang,et al.  Differential Lysosomal Proteolysis in Antigen-Presenting Cells Determines Antigen Fate , 2005, Science.

[82]  C. Figdor,et al.  Plasmacytoid dendritic cells of melanoma patients present exogenous proteins to CD4+ T cells after FcγRII-mediated uptake , 2006, The Journal of experimental medicine.

[83]  B. Barber,et al.  Adjuvant-free IgG responses induced with antigen coupled to antibodies against class II MHC , 1987, Nature.

[84]  R. Steinman,et al.  Dendritic Cell-Specific Intercellular Adhesion Molecule 3-Grabbing Nonintegrin/CD209 Is Abundant on Macrophages in the Normal Human Lymph Node and Is Not Required for Dendritic Cell Stimulation of the Mixed Leukocyte Reaction1 , 2005, The Journal of Immunology.

[85]  M. Groettrup,et al.  An Altered T Cell Repertoire in MECL-1-Deficient Mice1 , 2006, The Journal of Immunology.

[86]  F. Rey,et al.  Virus membrane-fusion proteins: more than one way to make a hairpin , 2006, Nature Reviews Microbiology.

[87]  A. Enk,et al.  Targeting of antigens to activated dendritic cells in vivo cures metastatic melanoma in mice. , 2005, Cancer research.

[88]  S. Gordon,et al.  Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. , 2004, Blood.

[89]  D. Weissman,et al.  Constitutive and induced expression of DC‐SIGN on dendritic cell and macrophage subpopulations in situ and in vitro , 2002, Journal of leukocyte biology.

[90]  S. Goldman,et al.  A new dendritic cell vaccine generated with interleukin-3 and interferon-β induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients , 2006, Cancer Immunology, Immunotherapy.

[91]  Ross M. Kedl,et al.  Immunization with HIV-1 Gag Protein Conjugated to a TLR7/8 Agonist Results in the Generation of HIV-1 Gag-Specific Th1 and CD8+ T Cell Responses , 2005, The Journal of Immunology.

[92]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[93]  R. Coffman,et al.  Toll-like receptor recognition regulates immunodominance in an antimicrobial CD4+ T cell response. , 2006, Immunity.

[94]  I. Moura,et al.  Identification of FcαRI as an Inhibitory Receptor that Controls Inflammation: Dual Role of FcRγ ITAM , 2005 .

[95]  Shizuo Akira,et al.  Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2 , 2003, The Journal of experimental medicine.

[96]  M. Udey,et al.  Dendritic Cells Transduced with Protein Antigens Induce Cytotoxic Lymphocytes and Elicit Antitumor Immunity1 , 2002, The Journal of Immunology.

[97]  V. Apostolopoulos,et al.  Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835] , 2006, Breast Cancer Research.

[98]  S. Jagannath,et al.  Bortezomib enhances dendritic cell (DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications. , 2007, Blood.

[99]  A. Barberis,et al.  An adenovirus vector with a chimeric fiber incorporating stabilized single chain antibody achieves targeted gene delivery , 2006, Gene Therapy.

[100]  S. Schwarze,et al.  In vivo protein transduction: delivery of a biologically active protein into the mouse. , 1999, Science.

[101]  J. Lisziewicz,et al.  Control of viral rebound through therapeutic immunization with DermaVir , 2005, AIDS.

[102]  E. Thiel,et al.  Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a phase I/II clinical trial , 2002, Cancer Immunology, Immunotherapy.

[103]  Yong‐jun Liu,et al.  Mouse and human dendritic cell subtypes , 2002, Nature Reviews Immunology.

[104]  D. Ladant,et al.  Anti-viral protection conferred by recombinant adenylate cyclase toxins from Bordetella pertussis carrying a CD8+ T cell epitope from lymphocytic choriomeningitis virus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[105]  M. Carrington,et al.  DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes , 2007, Proceedings of the National Academy of Sciences.

[106]  M. Bevan,et al.  Introduction of soluble protein into the class I pathway of antigen processing and presentation , 1988, Cell.

[107]  T. Curiel,et al.  High efficiency transduction of dendritic cells by adenoviral vectors targeted to DC-SIGN , 2005, Cancer biology & therapy.

[108]  E. Gilboa,et al.  Induction of carcinoembryonic antigen (cea)‐specific cytotoxic t‐lymphocyte responses In vitro using autologous dendritic cells loaded with cea peptide or cea rna in patients with metastatic malignancies expressing cea , 1999, International journal of cancer.

[109]  J. Yewdell,et al.  Cells process exogenous proteins for recognition by cytotoxic T lymphocytes. , 1988, Science.

[110]  C. Figdor,et al.  Migration of dendritic cell based cancer vaccines: in vivo veritas? , 2005, Current opinion in immunology.

[111]  T. Geijtenbeek,et al.  Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function , 2003, The Journal of experimental medicine.

[112]  M. Wright,et al.  Antigen delivery via two molecules on the CD8– dendritic cell subset induces humoral immunity in the absence of conventional “danger” , 2005, European journal of immunology.

[113]  Antonio Lanzavecchia,et al.  The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells1 , 2002, The Journal of Immunology.

[114]  Donna Niedzwiecki,et al.  Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. , 2003, Cancer research.

[115]  J. Lisziewicz,et al.  DermaVir: a novel topical vaccine for HIV/AIDS. , 2005, The Journal of investigative dermatology.

[116]  T. Curiel,et al.  Maturation of dendritic cells accompanies high-efficiency gene transfer by a CD40-targeted adenoviral vector. , 1999, Journal of immunology.

[117]  Dirk Schadendorf,et al.  Vaccination of melanoma patients with peptide- or tumorlysate-pulsed dendritic cells , 1998, Nature Medicine.

[118]  F. Hofhuis,et al.  Antigen targeting to myeloid-specific human Fc gamma RI/CD64 triggers enhanced antibody responses in transgenic mice. , 1996, The Journal of clinical investigation.

[119]  A. Enk,et al.  Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. , 2003, Blood.

[120]  Edgar G. Engleman,et al.  Vaccination of patients with B–cell lymphoma using autologous antigen–pulsed dendritic cells , 1996, Nature Medicine.

[121]  W. Jiskoot,et al.  Functional Characterization of an Endosome-disruptive Peptide and Its Application in Cytosolic Delivery of Immunoliposome-entrapped Proteins* , 2002, The Journal of Biological Chemistry.

[122]  Edgar G. Engleman,et al.  Dendritic Cells Injected Via Different Routes Induce Immunity in Cancer Patients1 , 2001, The Journal of Immunology.

[123]  A. Shaw,et al.  Triggering TLR signaling in vaccination. , 2006, Trends in immunology.

[124]  R. Steinman,et al.  Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses , 2006, The Journal of experimental medicine.

[125]  R. Steinman,et al.  Proliferating dendritic cell progenitors in human blood , 1994, The Journal of experimental medicine.

[126]  P. Hoffmann,et al.  Highly efficient antigen targeting to M-DC8+ dendritic cells via FcgammaRIII/CD16-specific antibody conjugates. , 2005, International immunology.

[127]  G. Nolan,et al.  Introduction of soluble proteins into the MHC class I pathway by conjugation to an HIV tat peptide. , 1997, Journal of immunology.

[128]  M. Wright,et al.  Molecular Cloning of F4/80-Like-Receptor, a Seven-Span Membrane Protein Expressed Differentially by Dendritic Cell and Monocyte-Macrophage Subpopulations1 2 , 2001, The Journal of Immunology.

[129]  Vincenzo Cerundolo,et al.  Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. , 2006, Blood.

[130]  Steven F Dowdy,et al.  Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis , 2004, Nature Medicine.

[131]  G. Heller,et al.  Mature Human Langerhans Cells Derived from CD34+ Hematopoietic Progenitors Stimulate Greater Cytolytic T Lymphocyte Activity in the Absence of Bioactive IL-12p70, by Either Single Peptide Presentation or Cross-Priming, Than Do Dermal-Interstitial or Monocyte-Derived Dendritic Cells. , 2005, The Journal of Immunology.

[132]  C. Figdor,et al.  Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[133]  K. Shortman,et al.  Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus, spleen, and lymph nodes. , 1997, Journal of immunology.

[134]  T. Ohno,et al.  Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells , 2001, Cancer Immunology, Immunotherapy.

[135]  R. Steinman,et al.  Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans. , 2002, Blood.

[136]  E. Bröcker,et al.  Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression. , 2002, Blood.

[137]  S. Tonegawa,et al.  Altered peptidase and viral-specific T cell response in LMP2 mutant mice. , 1994, Immunity.

[138]  R. Steinman,et al.  In Vivo Targeting of Antigens to Maturing Dendritic Cells via the DEC-205 Receptor Improves T Cell Vaccination , 2004, The Journal of experimental medicine.

[139]  D. Zelterman,et al.  An adenoviral vector cancer vaccine that delivers a tumor-associated antigen/CD40-ligand fusion protein to dendritic cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[140]  Corey Smith,et al.  A totally synthetic vaccine of generic structure that targets Toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[141]  C. Figdor,et al.  Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody. , 2005, Blood.

[142]  R. Steinman,et al.  Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. , 2001, Cancer research.

[143]  D. Accapezzato,et al.  Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo , 2005, The Journal of experimental medicine.

[144]  Nina Bhardwaj,et al.  Antigen-Specific Inhibition of Effector T Cell Function in Humans after Injection of Immature Dendritic Cells , 2001, The Journal of experimental medicine.

[145]  V. Apostolopoulos,et al.  Antibody and T cell responses of patients with adenocarcinoma immunized with mannan-MUC1 fusion protein. , 1997, The Journal of clinical investigation.

[146]  G. Bartsch,et al.  Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide , 2005, Cancer Immunology, Immunotherapy.

[147]  J. Peters,et al.  Immunotherapy of patients with hormone‐refractory prostate carcinoma pre‐treated with interferon‐gamma and vaccinated with autologous PSA‐peptide loaded dendritic cells—A pilot study , 2007, The Prostate.

[148]  D. Tarlinton,et al.  Antigen to the node: B cells go native. , 2007, Immunity.

[149]  C. Demangel,et al.  Targeting Dendritic Cells with Antigen-Containing Liposomes , 2004, Cancer Research.

[150]  A. Enk,et al.  A comparison of two types of dendritic cell as adjuvants for the induction of melanoma‐specific T‐cell responses in humans following intranodal injection , 2001, International journal of cancer.