Abstract
The unique antigen-presenting capabilities of dendritic cells (DCs) make them an attractive means with which to initiate an antitumor immune response. Using DCs transduced with tumor antigens for immunotherapy has several theoretical advantages over peptide-pulsed DCs including the possibility that transduced DCs are capable of presenting epitopes on both class I and class II MHC molecules. To test this theory, we inserted the human tumor antigen gp100 into mouse DCs transgenic for HLA-DRĪ²1*0401 using either adenoviral vector or a VSV-G pseudotyped retroviral vector. DCs transduced with tumor antigen were able to be recognized by both a murine CD8+ T-cell clone and a murine CD4+ T-cell line in a cytokine release assay, thereby demonstrating presentation of both MHC class I and class II gp100 epitopes. This study describes the simultaneous presentation of a tumor-associated antigen to both CD4+ and CD8+ T cells and lends support to the use of gene-modified DCs as a means to initiate both CD4+ and CD8+ antitumor responses.
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References
Rosenberg SA . Progress in human tumour immunology and immunotherapy Nature 2001 411: 380ā384
Rosenberg SA, Yang JC, Schwartzentruber DJ et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma Nat Med 1998 4: 321ā327
Rosenberg SA, Zhai Y, Yang JC et al. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens J Natl Cancer Inst 1998 90: 1894ā1900
Restifo NP, Ying H, Hwang L, Leitner WW . The promise of nucleic acid vaccines Gene Ther 2000 7: 89ā92
Banchereau J, Steinman RM . Dendritic cells and the control of immunity Nature 1998 392: 245ā252
Zitvogel L, Mayordomo JI, Tjandrawan T et al. Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines J Exp Med 1996 183: 87ā97
Paglia P, Chiodoni C, Rodolfo M, Colombo MP . Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo J Exp Med 1996 183: 317ā322
Specht JM, Wang G, Do MT et al. Dendritic cells retrovirally transduced with a model antigen gene are therapeutically effective against established pulmonary metastases J Exp Med 1997 186: 1213ā1221
Overwijk WW, Tsung A, Irvine KR et al. gp100/pmel 17 is a murine tumor rejection antigen: induction of āselfā-reactive, tumoricidal T cells using high-affinity, altered peptide ligand J Exp Med 1998 188: 277ā286
Touloukian CE, Leitner WW, Topalian SL et al. Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice J Immunol 2000 164: 3535ā3542
Ito K, Bian HJ, Molina M et al. HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis J Exp Med 1996 183: 2635ā2644
Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK . Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells Proc Natl Acad Sci USA 1993 90: 8033ā8037
Zhai Y, Yang JC, Kawakami Y et al. Antigen-specific tumor vaccines. Development and characterization of recombinant adenoviruses encoding MART1 or gp100 for cancer therapy J Immunol 1996 156: 700ā710
Lich JD, Elliott JF, Blum JS . Cytoplasmic processing is a prerequisite for presentation of an endogenous antigen by major histocompatibility complex class II proteins J Exp Med 2000 191: 1513ā1524
Kaplan JM, Yu Q, Piraino ST et al. Induction of antitumor immunity with dendritic cells transduced with adenovirus vector-encoding endogenous tumor-associated antigens J Immunol 1999 163: 699ā707
Morrison LA, Lukacher AE, Braciale VL, Fan DP, Braciale TJ . Differences in antigen presentation to MHC class I- and class II-restricted influenza virus-specific cytolytic T lymphocyte clones J Exp Med 1986 163: 903ā921
Jondal M, Schirmbeck R, Reimann J . MHC class I-restricted CTL responses to exogenous antigens Immunity 1996 5: 295ā302
Vijayasaradhi S, Xu Y, Bouchard B, Houghton AN . Intracellular sorting and targeting of melanosomal membrane proteins: identification of signals for sorting of the human brown locus protein, gp75 J Cell Biol 1995 130: 807ā820
Wang S, Bartido S, Yang G et al. A role for a melanosome transport signal in accessing the MHC class II presentation pathway and in eliciting CD4+ T cell responses J Immunol 1999 163: 5820ā5826
Wang RF, Wang X, Atwood AC, Topalian SL, Rosenberg SA . Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumor antigen Science 1999 284: 1351ā1354
Wu TC, Guarnieri FG, Staveley-O'Carroll KF et al. Engineering an intracellular pathway for major histocompatibility complex class II presentation of antigens Proc Natl Acad Sci USA 1995 92: 11671ā11675
Zarling AL, Ficarro SB, White FM, Shabanowitz J, Hunt DF, Engelhard VH . Phosphorylated peptides are naturally processed and presented by major histocompatibility complex class I molecules in vivo J Exp Med 2000 192: 1755ā1762
Haurum JS, Hoier IB, Arsequell G et al. Presentation of cytosolic glycosylated peptides by human class I major histocompatibilitycomplex molecules in vivo J Exp Med 1999 190: 145ā150
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Sloan, J., Kershaw, M., Touloukian, C. et al. MHC class I and class II presentation of tumor antigen in retrovirally and adenovirally transduced dendritic cells. Cancer Gene Ther 9, 946ā950 (2002). https://doi.org/10.1038/sj.cgt.7700509
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DOI: https://doi.org/10.1038/sj.cgt.7700509
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