Cancer Research Grants Metabolism and Cancer
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
[Cancer Research 59, 301-306, January 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rivoltini, L.
Right arrow Articles by Parmiani, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rivoltini, L.
Right arrow Articles by Parmiani, G.
[Cancer Research 59, 301-306, January 15, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

A Superagonist Variant of Peptide MART1/Melan A27–35 Elicits Anti-Melanoma CD8+ T Cells with Enhanced Functional Characteristics: Implication for More Effective Immunotherapy1

Licia Rivoltini2, Paola Squarcina, Douglas J. Loftus, Chiara Castelli, Paolo Tarsini, Arabella Mazzocchi, Francesca Rini, Vincenzo Viggiano, Filiberto Belli and Giorgio Parmiani

Divisions of Experimental Oncology D [L. R., P. S., C. C., P. T., A. M., F. R., G. P.], Medical Oncology A [V. V.], and Surgical Oncology B [F. B.], Istituto Nazionale Tumori, 20133 Milan, Italy, and Laboratory of Cell Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892 [D. J. L.]

In the present study, we show that a singly substituted peptide derived from the epitope MART127–35 and containing a Leu in position 1 (LAGIGILTV; 1L) behaves as a superagonist by in vitro inducing specific T cells with enhanced immunological functions. 1L-specific CTLs can be raised from peripheral blood of HLA-A2+ melanoma patients more efficiently than T cells specific for the cognate peptide. These T cells show a greater sensitivity to native MART127–35 when compared with CTL variable raised to parental peptide from the same patients. More importantly, anti-1L but not anti-native T cells display high levels of interferon {gamma} production at early time points, and readily secreted interleukin-2 in response to native epitope endogenously presented by melanoma cells. Additionally, anti-1L T cells are insensitive to the inhibitory effects of MART127–35 natural analogues that antagonize the lytic response of CTLs raised to the cognate peptide. Analysis of T-cell receptor variable ß usage suggests that the native and 1L peptides stimulate different components of the MART127–35-reactive T cell population. These data provide rationale to the use of superagonist analogues of tumor antigens for inducing in vivo immunization potentially able to overcome tumor immune escape and mediate a more significant control of tumor growth.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
E. Klechevsky, M. Gallegos, G. Denkberg, K. Palucka, J. Banchereau, C. Cohen, and Y. Reiter
Antitumor Activity of Immunotoxins with T-Cell Receptor-like Specificity against Human Melanoma Xenografts
Cancer Res., August 1, 2008; 68(15): 6360 - 6367.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. Johansen, T. Storni, L. Rettig, Z. Qiu, A. Der-Sarkissian, K. A. Smith, V. Manolova, K. S. Lang, G. Senti, B. Mullhaupt, et al.
Antigen kinetics determines immune reactivity
PNAS, April 1, 2008; 105(13): 5189 - 5194.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. E. Speiser, P. Baumgaertner, V. Voelter, E. Devevre, C. Barbey, N. Rufer, and P. Romero
Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen
PNAS, March 11, 2008; 105(10): 3849 - 3854.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Hou, B. Kavanagh, and L. Fong
Distinct CD8+ T Cell Repertoires Primed with Agonist and Native Peptides Derived from a Tumor-Associated Antigen
J. Immunol., February 1, 2008; 180(3): 1526 - 1534.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Eguchi, M. Hatano, F. Nishimura, X. Zhu, J. E. Dusak, H. Sato, I. F. Pollack, W. J. Storkus, and H. Okada
Identification of Interleukin-13 Receptor {alpha}2 Peptide Analogues Capable of Inducing Improved Antiglioma CTL Responses
Cancer Res., June 1, 2006; 66(11): 5883 - 5891.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Vertuani, A. Sette, J. Sidney, S. Southwood, J. Fikes, E. Keogh, J. A. Lindencrona, G. Ishioka, J. Levitskaya, and R. Kiessling
Improved Immunogenicity of an Immunodominant Epitope of the Her-2/neu Protooncogene by Alterations of MHC Contact Residues
J. Immunol., March 15, 2004; 172(6): 3501 - 3508.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. G. Carrabba, C. Castelli, M. J. Maeurer, P. Squarcina, A. Cova, L. Pilla, N. Renkvist, G. Parmiani, and L. Rivoltini
Suboptimal Activation of CD8+ T Cells by Melanoma-derived Altered Peptide Ligands: Role of Melan-A/MART-1 Optimized Analogues
Cancer Res., April 1, 2003; 63(7): 1560 - 1567.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Castilleja, D. Carter, C. L. Efferson, N. E. Ward, K. Kawano, B. Fisk, A. P. Kudelka, D. M. Gershenson, J. L. Murray, C. A. O'Brian, et al.
Induction of Tumor-Reactive CTL by C-Side Chain Variants of the CTL Epitope HER-2/neu Protooncogene (369-377) Selected by Molecular Modeling of the Peptide: HLA-A2 Complex
J. Immunol., October 1, 2002; 169(7): 3545 - 3554.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. Huarte, P. Sarobe, J. Lu, N. Casares, J. J. Lasarte, J. Dotor, M. Ruiz, J. Prieto, E. Celis, and F. Borras-Cuesta
Enhancing Immunogenicity of a CTL Epitope from Carcinoembryonic Antigen by Selective Amino Acid Replacements
Clin. Cancer Res., July 1, 2002; 8(7): 2336 - 2344.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
G. Parmiani, C. Castelli, P. Dalerba, R. Mortarini, L. Rivoltini, F. M. Marincola, and A. Anichini
Cancer Immunotherapy With Peptide-Based Vaccines: What Have We Achieved? Where Are We Going?
J Natl Cancer Inst, June 5, 2002; 94(11): 805 - 818.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. K. Hoffmann, D. J. Loftus, K. Nakano, M. J. Maeurer, K. Chikamatsu, E. Appella, T. L. Whiteside, and A. B. DeLeo
The Ability of Variant Peptides to Reverse the Nonresponsiveness of T Lymphocytes to the Wild-Type Sequence p53264-272 Epitope
J. Immunol., February 1, 2002; 168(3): 1338 - 1347.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J.-S. Blanchet, D. Valmori, I. Dufau, M. Ayyoub, C. Nguyen, P. Guillaume, B. Monsarrat, J.-C. Cerottini, P. Romero, and J. E. Gairin
A New Generation of Melan-A/MART-1 Peptides That Fulfill Both Increased Immunogenicity and High Resistance to Biodegradation: Implication for Molecular Anti-Melanoma Immunotherapy
J. Immunol., November 15, 2001; 167(10): 5852 - 5861.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. E. de Visser, T. A. Cordaro, H. W. H. G. Kessels, F. H. Tirion, T. N. M. Schumacher, and A. M. Kruisbeek
Low-Avidity Self-Specific T Cells Display a Pronounced Expansion Defect That Can Be Overcome by Altered Peptide Ligands
J. Immunol., October 1, 2001; 167(7): 3818 - 3828.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
S. Tangri, G. Y. Ishioka, X. Huang, J. Sidney, S. Southwood, J. Fikes, and A. Sette
Structural Features of Peptide Analogs of Human Histocompatibility Leukocyte Antigen Class I Epitopes that Are More Potent and Immunogenic than Wild-Type Peptide
J. Exp. Med., September 17, 2001; 194(6): 833 - 846.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Sliz, O. Michielin, J.-C. Cerottini, I. Luescher, P. Romero, M. Karplus, and D. C. Wiley
Crystal Structures of Two Closely Related but Antigenically Distinct HLA-A2/Melanocyte-Melanoma Tumor-Antigen Peptide Complexes
J. Immunol., September 15, 2001; 167(6): 3276 - 3284.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
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]

Home page
 J. Immunol.Home page
D. Valmori, V. Dutoit, D. Lienard, F. Lejeune, D. Speiser, D. Rimoldi, V. Cerundolo, P.-Y. Dietrich, J.-C. Cerottini, and P. Romero
Tetramer-Guided Analysis of TCR {beta}-Chain Usage Reveals a Large Repertoire of Melan-A-Specific CD8+ T Cells in Melanoma Patients
J. Immunol., July 1, 2000; 165(1): 533 - 538.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. N. J. Bullock, T. A. Colella, and V. H. Engelhard
The Density of Peptides Displayed by Dendritic Cells Affects Immune Responses to Human Tyrosinase and gp100 in HLA-A2 Transgenic Mice
J. Immunol., March 1, 2000; 164(5): 2354 - 2361.
[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
Copyright © 1999 by the American Association for Cancer Research.