| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Molecular Immunology Group, Tenovus Laboratory, Southampton University Hospitals Trust, Southampton, United Kingdom
DNA vaccines can activate immunity against tumor Ags expressed as
MHC class I-associated peptides. However, priming of CD8+
CTL against weak tumor Ags may require adjuvant molecules. We have used
a pathogen-derived sequence from tetanus toxin (fragment C (FrC)) fused
to tumor Ag sequences to promote Ab and CD4+ T cell
responses. For induction of CD8+ T cell responses, the FrC
sequence has been engineered to remove potentially competitive MHC
class I-binding epitopes and to improve presentation of tumor epitopes.
The colon carcinoma CT26 expresses an endogenous retroviral gene
product, gp70, containing a known H2-Ld-restricted epitope
(AH1). A DNA vaccine encoding gp70 alone was a poor inducer of CTL, and
performance was not significantly improved by fusion of full-length
FrC. However, use of a minimized domain of FrC, with the AH1 sequence
fused to the 3' position, led to rapid induction of high levels of CTL.
IFN-
-producing epitope-specific CTL were detectable ex vivo and
these killed CT26 targets in vitro. The single epitope vaccine was more
effective than GM-CSF-transfected CT26 tumor cells in inducing an
AH1-specific CTL response and equally effective in providing protection
against tumor challenge. Levels of AH1-specific CTL in vivo were
increased following injection of tumor cells, and CTL expanded in vitro
were able to kill CT26 cells in tumor bearers. Pre-existing immunity to
tetanus toxoid had no effect on the induction of AH1-specific CTL.
These data demonstrate the power of epitope-specific CTL against tumor
cells and illustrate a strategy for priming immunity via a dual
component DNA vaccine.
This article has been cited by other articles:
|
|
 |
|
  H. Sugiyama Expectation for DNA leukemia vaccines Blood, October 1, 2008; 112(7): 2602 - 2602. [Full Text] [PDF]
|
|
|
|
|
|
C. Chaise, S. L. Buchan, J. Rice, J. Marquet, H. Rouard, M. Kuentz, G. E. Vittes, V. Molinier-Frenkel, J.-P. Farcet, H. J. Stauss, et al. DNA vaccination induces WT1-specific T-cell responses with potential clinical relevance Blood, October 1, 2008; 112(7): 2956 - 2964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Radcliffe, J. S. Roddick, P. S. Friedmann, F. K. Stevenson, and S. M. Thirdborough Prime-Boost with Alternating DNA Vaccines Designed to Engage Different Antigen Presentation Pathways Generates High Frequencies of Peptide-Specific CD8+ T Cells J. Immunol., November 15, 2006; 177(10): 6626 - 6633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schirmbeck, P. Riedl, M. Kupferschmitt, U. Wegenka, H. Hauser, J. Rice, A. Kroger, and J. Reimann Priming Protective CD8 T Cell Immunity by DNA Vaccines Encoding Chimeric, Stress Protein-Capturing Tumor-Associated Antigen J. Immunol., August 1, 2006; 177(3): 1534 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rice, S. Dunn, K. Piper, S. L. Buchan, P. A. Moss, and F. K. Stevenson DNA Fusion Vaccines Induce Epitope-Specific Cytotoxic CD8+ T Cells against Human Leukemia-Associated Minor Histocompatibility Antigens. Cancer Res., May 15, 2006; 66(10): 5436 - 5442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gerloni, P. Castiglioni, and M. Zanetti The Cooperation between Two CD4 T Cells Induces Tumor Protective Immunity in MUC.1 Transgenic Mice J. Immunol., November 15, 2005; 175(10): 6551 - 6559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Savelyeva, C. A. King, E. S. Vitetta, and F. K. Stevenson Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help PNAS, August 2, 2005; 102(31): 10987 - 10992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Buchan, E. Gronevik, I. Mathiesen, C. A. King, F. K. Stevenson, and J. Rice Electroporation as a "Prime/Boost" Strategy for Naked DNA Vaccination against a Tumor Antigen J. Immunol., May 15, 2005; 174(10): 6292 - 6298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. K. Stevenson, C. H. Ottensmeier, P. Johnson, D. Zhu, S. L. Buchan, K. J. McCann, J. S. Roddick, A. T. King, F. McNicholl, N. Savelyeva, et al. DNA vaccines to attack cancer PNAS, October 5, 2004; 101(suppl_2): 14646 - 14652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rice, S. Buchan, H. Dewchand, E. Simpson, and F. K. Stevenson DNA Fusion Vaccines Induce Targeted Epitope-Specific CTLs against Minor Histocompatibility Antigens from a Normal or Tolerized Repertoire J. Immunol., October 1, 2004; 173(7): 4492 - 4499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. Heslop, F. K. Stevenson, and J. J. Molldrem Immunotherapy of Hematologic Malignancy Hematology, January 1, 2003; 2003(1): 331 - 349. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
