| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Tenovus Laboratory, Molecular Immunology Group, and
Cancer Sciences Centre, Southampton University Hospitals Trust, Southampton, United Kingdom.
DNA vaccination offers a strategy to induce immune attack on cancer cells, but tumor Ags are often weak. Inclusion of a "foreign" protein increases immunogenicity, and we found previously that fusion of the fragment C (FrC) of tetanus toxin to the tumor Ag sequence promotes Ab and CD4+ responses against B cell tumors. For CTL responses, use of the full two-domain FrC may be less helpful, because known immunogenic MHC class I-binding peptides in the second domain could compete with attached tumor-derived epitopes. Therefore, we removed the second domain, retaining the N-terminal domain, which contains a "universal" helper epitope. We investigated the ability to induce CTL responses of candidate peptides placed at the C terminus of this domain. As test peptides, we repositioned the two known CTL motifs from the second domain to this site. Strong CTL responses to each peptide were induced by the engineered construct, as compared with the native FrC construct. Induced CTLs were able to specifically kill tumor cells transfected with FrC as a surrogate tumor Ag both in vitro and in vivo. Further reduction of the domain to a short helper epitope generated only weak CTL responses against fused peptides, and synthetic peptides mixed with the plasmid containing the first domain were ineffective. The single FrC domain-peptide vaccine design also was able to induce high levels of CTLs against a known epitope from carcinoembryonic Ag. Response to peptide was suppressed if two FrC domains were present, consistent with immunodominance. These principles and designs may have relevance for cancer vaccines delivered via DNA.
This article has been cited by other articles:
|
|
 |
|
  W. W. Leitner, M. C. Baker, T. L. Berenberg, M. C. Lu, P. J. Yannie, and M. C. Udey Enhancement of DNA tumor vaccine efficacy by gene gun-mediated codelivery of threshold amounts of plasmid-encoded helper antigen Blood, January 1, 2009; 113(1): 37 - 45. [Abstract] [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. Rice, S. Buchan, and F. K. Stevenson Critical Components of a DNA Fusion Vaccine Able to Induce Protective Cytotoxic T Cells Against a Single Epitope of a Tumor Antigen J. Immunol., October 1, 2002; 169(7): 3908 - 3913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Wolkers, M. Toebes, M. Okabe, J. B. A. G. Haanen, and T. N. M. Schumacher Optimizing the Efficacy of Epitope-Directed DNA Vaccination J. Immunol., May 15, 2002; 168(10): 4998 - 5004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nishikawa, K. Tanida, H. Ikeda, M. Sakakura, Y. Miyahara, T. Aota, K. Mukai, M. Watanabe, K. Kuribayashi, L. J. Old, et al. Role of SEREX-defined immunogenic wild-type cellular molecules in the development of tumor-specific immunity PNAS, December 4, 2001; 98(25): 14571 - 14576. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
