| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Immunology |
Department of Immunology, Mayo Clinic and Mayo Graduate School, Rochester, Minnesota 55905
Although peptide immunization often leads to the induction of strong T-cell responses, it is seldom effective against established tumors. One possibility is that these T-cell responses are not strong enough or do not last sufficiently long to have an effect in tumor eradication. Here, we examined the role of synthetic oligodeoxynucleotide (ODN) adjuvants containing unmethylated cytosine-guanine motifs (CpG-ODN) and CTLA-4 blockade in enhancing the antitumor effectiveness of peptide vaccines intended to elicit CTL responses. The results show that combination immunotherapy consisting of vaccination with a synthetic peptide corresponding to an immunodominant CTL epitope derived from tyrosinase-related protein-2 administered with CpG-ODN adjuvant and followed by systemic injection of anti-CTLA-4 antibodies increased the survival of mice against the poorly immunogenic B16 melanoma. Interestingly, whereas this combination therapy was effective when administered to tumor-bearing mice (therapeutic protocol), it had no significant effect when applied in the prophylactic mode (i.e., before the tumor challenge). Moreover, the antitumor effect of the combination immunotherapy required the participation of CD4+ and CD8+ T lymphocytes and was accompanied by the induction of antitumor CD4+ T-cell responses. The overall results suggest that peptide vaccination of tumor-bearing mice, applied in combination with a strong adjuvant and CTLA-4 blockade, is capable of eliciting durable antitumor T cell responses that provide survival benefit. These findings bear clinical significance for the design of peptide-based therapeutic vaccines for human cancer patients.
This article has been cited by other articles:
|
|
 |
|
  M. Kortylewski, M. Kujawski, A. Herrmann, C. Yang, L. Wang, Y. Liu, R. Salcedo, and H. Yu Toll-like Receptor 9 Activation of Signal Transducer and Activator of Transcription 3 Constrains Its Agonist-Based Immunotherapy Cancer Res., March 15, 2009; 69(6): 2497 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Fong and E. J. Small Anti-Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment J. Clin. Oncol., November 10, 2008; 26(32): 5275 - 5283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Asprodites, L. Zheng, D. Geng, C. Velasco-Gonzalez, L. Sanchez-Perez, and E. Davila Engagement of Toll-like receptor-2 on cytotoxic T-lymphocytes occurs in vivo and augments antitumor activity FASEB J, October 1, 2008; 22(10): 3628 - 3637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. N. Haining, J. Davies, H. Kanzler, L. Drury, T. Brenn, J. Evans, J. Angelosanto, S. Rivoli, K. Russell, S. George, et al. CpG Oligodeoxynucleotides Alter Lymphocyte and Dendritic Cell Trafficking in Humans Clin. Cancer Res., September 1, 2008; 14(17): 5626 - 5634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zheng, N. Asprodites, A. H. Keene, P. Rodriguez, K. D. Brown, and E. Davila TLR9 engagement on CD4 T lymphocytes represses {gamma}-radiation-induced apoptosis through activation of checkpoint kinase response elements Blood, March 1, 2008; 111(5): 2704 - 2713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Kochenderfer and R. E. Gress A Comparison and Critical Analysis of Preclinical Anticancer Vaccination Strategies Exp Biol Med, October 1, 2007; 232(9): 1130 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Kochenderfer, J. L. Simpson, C. D. Chien, and R. E. Gress Vaccination regimens incorporating CpG-containing oligodeoxynucleotides and IL-2 generate antigen-specific antitumor immunity from T-cell populations undergoing homeostatic peripheral expansion after BMT Blood, July 1, 2007; 110(1): 450 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Kochenderfer, C. D. Chien, J. L. Simpson, and R. E. Gress Synergism between CpG-Containing Oligodeoxynucleotides and IL-2 Causes Dramatic Enhancement of Vaccine-Elicited CD8+ T Cell Responses J. Immunol., December 15, 2006; 177(12): 8860 - 8873. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. M. Belyakov, D. Isakov, Q. Zhu, A. Dzutsev, D. Klinman, and J. A. Berzofsky Enhancement of CD8+ T Cell Immunity in the Lung by CpG Oligodeoxynucleotides Increases Protective Efficacy of a Modified Vaccinia Ankara Vaccine against Lethal Poxvirus Infection Even in a CD4-Deficient Host J. Immunol., November 1, 2006; 177(9): 6336 - 6343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-F. Bai, J.-Q. Liu, P. S. Joshi, L. Wang, L. Yin, J. Labanowska, N. Heerema, P. Zheng, and Y. Liu Different Lineages of P1A-Expressing Cancer Cells Use Divergent Modes of Immune Evasion for T-Cell Adoptive Therapy Cancer Res., August 15, 2006; 66(16): 8241 - 8249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wakita, K. Chamoto, Y. Zhang, Y. Narita, D. Noguchi, H. Ohnishi, T. Iguchi, T. Sakai, H. Ikeda, and T. Nishimura An indispensable role of type-1 IFNs for inducing CTL-mediated complete eradication of established tumor tissue by CpG-liposome co-encapsulated with model tumor antigen Int. Immunol., March 1, 2006; 18(3): 425 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Maker, P. Attia, and S. A. Rosenberg Analysis of the Cellular Mechanism of Antitumor Responses and Autoimmunity in Patients Treated with CTLA-4 Blockade J. Immunol., December 1, 2005; 175(11): 7746 - 7754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Weihrauch, S. Ansen, E. Jurkiewicz, C. Geisen, Z. Xia, K. S. Anderson, E. Gracien, M. Schmidt, B. Wittig, V. Diehl, et al. Phase I/II Combined Chemoimmunotherapy with Carcinoembryonic Antigen-Derived HLA-A2-Restricted CAP-1 Peptide and Irinotecan, 5-Fluorouracil, and Leucovorin in Patients with Primary Metastatic Colorectal Cancer Clin. Cancer Res., August 15, 2005; 11(16): 5993 - 6001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Paschen, M. Song, W. Osen, X. D. Nguyen, J. Mueller-Berghaus, D. Fink, N. Daniel, M. Donzeau, W. Nagel, H. Kropshofer, et al. Detection of Spontaneous CD4+ T-Cell Responses in Melanoma Patients against a Tyrosinase-Related Protein-2-Derived Epitope Identified in HLA-DRB1*0301 Transgenic Mice Clin. Cancer Res., July 15, 2005; 11(14): 5241 - 5247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sanderson, R. Scotland, P. Lee, D. Liu, S. Groshen, J. Snively, S. Sian, G. Nichol, T. Davis, T. Keler, et al. Autoimmunity in a Phase I Trial of a Fully Human Anti-Cytotoxic T-Lymphocyte Antigen-4 Monoclonal Antibody With Multiple Melanoma Peptides and Montanide ISA 51 for Patients With Resected Stages III and IV Melanoma J. Clin. Oncol., February 1, 2005; 23(4): 741 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Demaria, N. Kawashima, A. M. Yang, M. L. Devitt, J. S. Babb, J. P. Allison, and S. C. Formenti Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast Cancer Clin. Cancer Res., January 15, 2005; 11(2): 728 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Suzuki, D. Wakita, K. Chamoto, Y. Narita, T. Tsuji, T. Takeshima, H. Gyobu, Y. Kawarada, S. Kondo, S. Akira, et al. Liposome-Encapsulated CpG Oligodeoxynucleotides as a Potent Adjuvant for Inducing Type 1 Innate Immunity Cancer Res., December 1, 2004; 64(23): 8754 - 8760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Daftarian, G.-Y. Song, S. Ali, M. Faynsod, J. Longmate, D. J. Diamond, and J. D. I. Ellenhorn Two Distinct Pathways of Immuno-Modulation Improve Potency of p53 Immunization in Rejecting Established Tumors Cancer Res., August 1, 2004; 64(15): 5407 - 5414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gregoire, C. Logre, P. Metharom, E. Loing, J. Chomilier, M. B. Rosset, P. Aucouturier, and C. Carnaud Identification of two immunogenic domains of the prion protein--PrP--which activate class II-restricted T cells and elicit antibody responses against the native molecule J. Leukoc. Biol., July 1, 2004; 76(1): 125 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Garbi, B. Arnold, S. Gordon, G. J. Hammerling, and R. Ganss CpG Motifs as Proinflammatory Factors Render Autochthonous Tumors Permissive for Infiltration and Destruction J. Immunol., May 15, 2004; 172(10): 5861 - 5869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Rosset, C. Ballerini, S. Gregoire, P. Metharom, C. Carnaud, and P. Aucouturier Breaking Immune Tolerance to the Prion Protein Using Prion Protein Peptides Plus Oligodeoxynucleotide-CpG in Mice J. Immunol., May 1, 2004; 172(9): 5168 - 5174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lu, Y. Higashimoto, E. Appella, and E. Celis Multiepitope Trojan Antigen Peptide Vaccines for the Induction of Antitumor CTL and Th Immune Responses J. Immunol., April 1, 2004; 172(7): 4575 - 4582. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
