| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Hematology-Oncology Unit and
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 and Department of Medicine, Harvard Medical School, Boston, MA 02114; and
Genzyme Molecular Oncology, Framingham, MA 01701
Replication-deficient recombinant adenovirus (Ad) encoding human
gp100 or MART-1 melanoma Ag was used to transduce human dendritic cells
(DC) ex vivo as a model system for cancer vaccine therapy. A second
generation E1/E4 region deleted Ad which harbors the CMV
immediate-early promoter/enhancer and a unique E4-ORF6/pIX chimeric
gene was employed as the backbone vector. We demonstrate that human
monocyte-derived DC are permissive to Ad infection at multiplicity of
infection between 100 and 500 and occurs independent of the coxsackie
Ad receptor. Fluorescent-labeled Ad was used to assess the kinetics and
distribution of viral vector within DC. Ad-transduced DC show peak
transgene expression at 24–48 h and expression remains detectable for
at least 7 days. DC transduced with replication-deficient Ad do not
exhibit any unusual phenotypic characteristics or cytopathic effects.
DC transduced with Ad2/gp100v2 can elicit tumor-specific CTL in vitro
from patients bearing gp100+ metastatic melanoma. Using a
panel of gp100-derived synthetic peptides, we show that
Ad2/gp100v2-transduced DC elicit Ag-specific CTL that recognize only
the G209 and G280 epitopes, both of which display relatively short
half-lives (
7–8 h) on the surface of HLA-A*0201+ cells.
Thus, patients with metastatic melanoma are not tolerant to gp100 Ag
based on the detection of CD8+ T cells specific for
multiple HLA-A*0201-restricted, gp100-derived
epitopes.
This article has been cited by other articles:
|
|
 |
|
  M. A. Purbhoo, Y. Li, D. H. Sutton, J. E. Brewer, E. Gostick, G. Bossi, B. Laugel, R. Moysey, E. Baston, N. Liddy, et al. The HLA A*0201-restricted hTERT540-548 peptide is not detected on tumor cells by a CTL clone or a high-affinity T-cell receptor Mol. Cancer Ther., July 1, 2007; 6(7): 2081 - 2091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chapiro, S. Claverol, F. Piette, W. Ma, V. Stroobant, B. Guillaume, J.-E. Gairin, S. Morel, O. Burlet-Schiltz, B. Monsarrat, et al. Destructive Cleavage of Antigenic Peptides Either by the Immunoproteasome or by the Standard Proteasome Results in Differential Antigen Presentation J. Immunol., January 15, 2006; 176(2): 1053 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Linette, D. Zhang, F. S. Hodi, E. P. Jonasch, S. Longerich, C. P. Stowell, I. J. Webb, H. Daley, R. J. Soiffer, A. M. Cheung, et al. Immunization Using Autologous Dendritic Cells Pulsed with the Melanoma-Associated Antigen gp100-Derived G280-9V Peptide Elicits CD8+ Immunity Clin. Cancer Res., November 1, 2005; 11(21): 7692 - 7699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yang, K.-Y. Tsang, and J. Schlom Induction of Higher-Avidity Human CTLs by Vector-Mediated Enhanced Costimulation of Antigen-Presenting Cells Clin. Cancer Res., August 1, 2005; 11(15): 5603 - 5615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yang and F. G. Haluska Treatment of Melanoma with 5-Fluorouracil or Dacarbazine In Vitro Sensitizes Cells to Antigen-Specific CTL Lysis through Perforin/Granzyme- and Fas-Mediated Pathways J. Immunol., April 1, 2004; 172(7): 4599 - 4608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mukouyama, N. K. Janzen, J. M. Hernandez, J. S. Lam, R. Caliliw, A. Y. Wang, R. A. Figlin, A. S. Belldegrun, and G. Zeng Generation of Kidney Cancer-Specific Antitumor Immune Responses Using Peripheral Blood Monocytes Transduced With a Recombinant Adenovirus Encoding Carbonic Anhydrase 9 Clin. Cancer Res., February 15, 2004; 10(4): 1421 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tuettenberg, H. Jonuleit, T. Tuting, J. Bruck, V. Biermann, S. Kochanek, J. Knop, and A. H. Enk Early Adenoviral Gene Expression Mediates Immunosuppression by Transduced Dendritic Cell (DC): Implications for Immunotherapy Using Genetically Modified DC J. Immunol., February 1, 2004; 172(3): 1524 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Parkhurst, C. DePan, J. P. Riley, S. A. Rosenberg, and S. Shu Hybrids of Dendritic Cells and Tumor Cells Generated by Electrofusion Simultaneously Present Immunodominant Epitopes from Multiple Human Tumor-Associated Antigens in the Context of MHC Class I and Class II Molecules J. Immunol., May 15, 2003; 170(10): 5317 - 5325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yang, G. P. Linette, S. Longerich, and F. G. Haluska Antimelanoma Activity of CTL Generated from Peripheral Blood Mononuclear Cells After Stimulation with Autologous Dendritic Cells Pulsed with Melanoma gp100 Peptide G209-2M Is Correlated to TCR Avidity J. Immunol., July 1, 2002; 169(1): 531 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tsao, P. Millman, G. P. Linette, F. S. Hodi, A. J. Sober, M. A. Goldberg, and F. G. Haluska Hypopigmentation Associated With an Adenovirus-Mediated gp100/MART-1-Transduced Dendritic Cell Vaccine for Metastatic Melanoma Arch Dermatol, June 1, 2002; 138(6): 799 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kirkwood, J. G. Ibrahim, J. A. Sosman, V. K. Sondak, S. S. Agarwala, M. S. Ernstoff, and U. Rao High-Dose Interferon Alfa-2b Significantly Prolongs Relapse-Free and Overall Survival Compared With the GM2-KLH/QS-21 Vaccine in Patients With Resected Stage IIB-III Melanoma: Results of Intergroup Trial E1694/S9512/C509801 J. Clin. Oncol., May 1, 2001; 19(9): 2370 - 2380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Rea, M. J. E. Havenga, M. van den Assem, R. P. M. Sutmuller, A. Lemckert, R. C. Hoeben, A. Bout, C. J. M. Melief, and R. Offringa Highly Efficient Transduction of Human Monocyte-Derived Dendritic Cells with Subgroup B Fiber-Modified Adenovirus Vectors Enhances Transgene-Encoded Antigen Presentation to Cytotoxic T Cells J. Immunol., April 15, 2001; 166(8): 5236 - 5244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vincent, B.-G. Harvey, S. M. Hogan, C. J. Bailey, R. G. Crystal, and P. L. Leopold Rapid Assessment of Adenovirus Serum Neutralizing Antibody Titer Based on Quantitative, Morphometric Evaluation of Capsid Binding and Intracellular Trafficking: Population Analysis of Adenovirus Capsid Association with Cells Is Predictive of Adenovirus Infectivity J. Virol., February 1, 2001; 75(3): 1516 - 1521. [Abstract] [Full Text]
|
|
|
|
|
|
S. Stager, D. F. Smith, and P. M. Kaye Immunization with a Recombinant Stage-Regulated Surface Protein from Leishmania donovani Induces Protection Against Visceral Leishmaniasis J. Immunol., December 15, 2000; 165(12): 7064 - 7071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Russell Update on adenovirus and its vectors J. Gen. Virol., November 1, 2000; 81(11): 2573 - 2604. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
