| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
In a recent clinical trial, HLA-A2+ melanoma patients were vaccinated with a peptide derived from the melanoma Ag gp100, which had been modified at the second position (g9-209 2M) to enhance MHC binding affinity. Vaccination led to a significant increase in lymphocyte precursors in 10 of 11 patients but did not result in objective cancer responses. We observed that some postvaccination PBMC cultures were less reactive with tumor cells than they were with g9-209 peptide-pulsed T2 cells. In contrast, g9-209-reactive tumor-infiltrating lymphocyte cultures generally reacted equally with tumor cells and g9-209 peptide-pulsed T2 cells. To investigate this difference in T cell reactivity, T cell cloids derived from the PBMC of three patients vaccinated with g9-209 2M were compared with T cell cloids isolated from g9-209-reactive TIL cultures. All of the T cell cloids obtained from TIL reacted with HLA-A2+, gp100+ melanoma cell lines as well as with g9-209 and g9-209 2M peptide-pulsed targets. In contrast, only 3 of 20 PBMC-derived T cell cloids reacted with melanoma cell lines in addition to g9-209 and to g9-209 2M peptide-pulsed targets. Twelve of twenty PBMC-derived cloids reacted with g9-209 and g9-209 2M peptide-pulsed targets but not with melanoma cell lines. And 5 of 20 PBMC-derived cloids recognized only the g9-209 2M-modified peptide-pulsed targets. These results suggest that immunizing patients with the modified peptide affected the T cell repertoire by expanding an array of T cells with different fine specificities, only some of which recognized melanoma cells.
This article has been cited by other articles:
|
|
 |
|
  S. Wieckowski, P. Baumgaertner, P. Corthesy, V. Voelter, P. Romero, D. E. Speiser, and N. Rufer Fine Structural Variations of {alpha}{beta}TCRs Selected by Vaccination with Natural versus Altered Self-Antigen in Melanoma Patients J. Immunol., October 15, 2009; 183(8): 5397 - 5406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. A. McWilliams, S. M. McGurran, S. W. Dow, J. E. Slansky, and R. M. Kedl A Modified Tyrosinase-Related Protein 2 Epitope Generates High-Affinity Tumor-Specific T Cells but Does Not Mediate Therapeutic Efficacy in an Intradermal Tumor Model J. Immunol., July 1, 2006; 177(1): 155 - 161. [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]
|
|
|
|
|
|
O. Y. Borbulevych, T. K. Baxter, Z. Yu, N. P. Restifo, and B. M. Baker Increased Immunogenicity of an Anchor-Modified Tumor-Associated Antigen Is Due to the Enhanced Stability of the Peptide/MHC Complex: Implications for Vaccine Design J. Immunol., April 15, 2005; 174(8): 4812 - 4820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ida, S. Kawaguchi, Y. Sato, T. Tsukahara, Y. Nabeta, H. Sahara, H. Ikeda, T. Torigoe, S. Ichimiya, K. Kamiguchi, et al. Crisscross CTL Induction by SYT-SSX Junction Peptide and Its HLA-A*2402 Anchor Substitute J. Immunol., July 15, 2004; 173(2): 1436 - 1443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
V. Ramakrishna, J. F. Treml, L. Vitale, J. E. Connolly, T. O'Neill, P. A. Smith, C. L. Jones, L.-Z. He, J. Goldstein, P. K. Wallace, et al. Mannose Receptor Targeting of Tumor Antigen pmel17 to Human Dendritic Cells Directs Anti-Melanoma T Cell Responses via Multiple HLA Molecules J. Immunol., March 1, 2004; 172(5): 2845 - 2852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Denkberg, E. Klechevsky, and Y. Reiter Modification of a Tumor-Derived Peptide at an HLA-A2 Anchor Residue Can Alter the Conformation of the MHC-Peptide Complex: Probing with TCR-Like Recombinant Antibodies J. Immunol., October 15, 2002; 169(8): 4399 - 4407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Z. Wang, R. Turner, B. M. Baker, and W. E. Biddison MHC Allele-Specific Molecular Features Determine Peptide/HLA-A2 Conformations That Are Recognized by HLA-A2-Restricted T Cell Receptors J. Immunol., September 15, 2002; 169(6): 3146 - 3154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Lawendowski, G. M. Giurleo, Y. Y. Huang, G. J. Franklin, J. M. Kaplan, B. L. Roberts, and C. A. Nicolette Solid-Phase Epitope Recovery: A High Throughput Method for Antigen Identification and Epitope Optimization J. Immunol., September 1, 2002; 169(5): 2414 - 2421. [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]
|
|
|
|
 |
|
 M. A. Haque, P. Li, S. K. Jackson, H. M. Zarour, J. W. Hawes, U. T. Phan, M. Maric, P. Cresswell, and J. S. Blum Absence of {gamma}-Interferon-inducible Lysosomal Thiol Reductase in Melanomas Disrupts T Cell Recognition of Select Immunodominant Epitopes J. Exp. Med., May 20, 2002; 195(10): 1267 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Valmori, V. Dutoit, V. Schnuriger, A.-L. Quiquerez, M. J. Pittet, P. Guillaume, V. Rubio-Godoy, P. R. Walker, D. Rimoldi, D. Lienard, et al. Vaccination with a Melan-A Peptide Selects an Oligoclonal T Cell Population with Increased Functional Avidity and Tumor Reactivity J. Immunol., April 15, 2002; 168(8): 4231 - 4240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Buteau, S. N. Markovic, and E. Celis Challenges in the Development of Effective Peptide Vaccines for Cancer Mayo Clin. Proc., April 1, 2002; 77(4): 339 - 349. [Abstract] [PDF]
|
|
|
|
|
|
R. B. Mailliard, S. Egawa, Q. Cai, A. Kalinska, S. N. Bykovskaya, M. T. Lotze, M. L. Kapsenberg, W. J. Storkus, and P. Kalinski Complementary Dendritic Cell-activating Function of CD8+ and CD4+ T Cells: Helper Role of CD8+ T Cells in the Development of T Helper Type 1 Responses J. Exp. Med., February 19, 2002; 195(4): 473 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Ostrov, M. M. Roden, W. Shi, E. Palmieri, G. J. Christianson, L. Mendoza, G. Villaflor, D. Tilley, N. Shastri, H. Grey, et al. How H13 Histocompatibility Peptides Differing by a Single Methyl Group and Lacking Conventional MHC Binding Anchor Motifs Determine Self-Nonself Discrimination J. Immunol., January 1, 2002; 168(1): 283 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Rosa, R. Krishnan, S. Markel, J. P. Schneck, R. Houghten, C. Pinilla, and D. J. Diamond Enhanced immune activity of cytotoxic T-lymphocyte epitope analogs derived from positional scanning synthetic combinatorial libraries Blood, March 15, 2001; 97(6): 1776 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Anderson, G. E. Peoples, J. L. Murray, M. A. Gillogly, D. M. Gershenson, and C. G. Ioannides Peptide Priming of Cytolytic Activity to HER-2 Epitope 369-377 in Healthy Individuals Clin. Cancer Res., November 1, 2000; 6(11): 4192 - 4200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M. I. Nishimura, D. Avichezer, M. C. Custer, C. S. Lee, C. Chen, M. R. Parkhurst, R. A. Diamond, P. F. Robbins, D. J. Schwartzentruber, and S. A. Rosenberg MHC Class I-restricted Recognition of a Melanoma Antigen by a Human CD4+ Tumor Infiltrating Lymphocyte Cancer Res., December 1, 1999; 59(24): 6230 - 6238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Peoples, B. W. Anderson, T. V. Lee, J. L. Murray, A. P. Kudelka, J. T. Wharton, and C. G. Ioannides Vaccine Implications of Folate Binding Protein, a Novel Cytotoxic T Lymphocyte-recognized Antigen System in Epithelial Cancers Clin. Cancer Res., December 1, 1999; 5(12): 4214 - 4223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Sharma, J. J. Kuhns, S. Yan, R. H. Friedline, B. Long, R. Tisch, and E. J. Collins Class I Major Histocompatibility Complex Anchor Substitutions Alter the Conformation of T Cell Receptor Contacts J. Biol. Chem., June 8, 2001; 276(24): 21443 - 21449. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
