Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO Subscriptions PDA Services My JCO Customer Service

Originally published as JCO Early Release 10.1200/JCO.2005.06.205 on August 8 2005

Journal of Clinical Oncology, Vol 23, No 25 (September 1), 2005: pp. 6043-6053
© 2005 American Society of Clinical Oncology.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
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 Save to my personal folders
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Attia, P.
Right arrow Articles by Rosenberg, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Attia, P.
Right arrow Articles by Rosenberg, S. A.
Related Articles
Right arrowRelated Editorial

Autoimmunity Correlates With Tumor Regression in Patients With Metastatic Melanoma Treated With Anti–Cytotoxic T-Lymphocyte Antigen-4

Peter Attia, Giao Q. Phan, Ajay V. Maker, Michael R. Robinson, Martha M. Quezado, James C. Yang, Richard M. Sherry, Suzanne L. Topalian, Udai S. Kammula, Richard E. Royal, Nicholas P. Restifo, Leah R. Haworth, Catherine Levy, Sharon A. Mavroukakis, Geoff Nichol, Michael J. Yellin, Steven A. Rosenberg

From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and Medarex Inc, Princeton, NJ

Address reprint requests to Steven A. Rosenberg, MD, PhD, Surgery Branch, National Cancer Institute, National Institutes of Health, CRC, Room 3W-3940, 10 Center Dr, Bethesda, MD 20892-1201; e-mail: sar{at}nih.gov

PURPOSE: Previously, we reported our experience treating 14 patients with metastatic melanoma using a fully human antibody to cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) in conjunction with peptide vaccination. We have now treated 56 patients to evaluate two different dose schedules of anti–CTLA-4 and to explore the relationship between autoimmunity and tumor regression.

PATIENTS AND METHODS: A total of 56 patients with progressive stage IV melanoma were enrolled onto the study. All had Karnofsky performance status ≥ 60% with no prior history of autoimmunity. Twenty-nine patients received 3 mg/kg anti–CTLA-4 every 3 weeks, whereas 27 received 3 mg/kg as their initial dose with subsequent doses reduced to 1 mg/kg every 3 weeks. In both cohorts patients received concomitant vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V).

RESULTS: Two patients achieved a complete response (ongoing at 30 and 31 months, respectively) and five patients achieved a partial response (durations of 4, 6, 25+, 26+, and 34+ months, respectively), for an overall objective response rate of 13%. Tumor regression was seen in lung, liver, brain, lymph nodes, and subcutaneous sites. Of 14 patients with grade 3/4 autoimmune toxicity, five (36%) experienced a clinical response compared with only two responses in the 42 patients (5%) with no autoimmune toxicity (P = .008). There were no significant differences in response rate or toxicity between the two dose schedules.

CONCLUSION: Administration of anti–CTLA-4 monoclonal antibody plus peptide vaccination can cause durable objective responses, which correlate with the induction of autoimmunity, in patients with metastatic melanoma.

Authors' disclosures of potential conflicts of interest are found at the end of this article.


Related Editorial

  • Self-Recognition and Tumor Response to Immunotherapy
    Marc S. Ernstoff
    JCO 2005 23: 5875-5877 [Full Text]


This article has been cited by other articles:


Home page
Clin. Cancer Res.Home page
P. Correale, P. Tagliaferri, A. Fioravanti, M. T. Del Vecchio, C. Remondo, F. Montagnani, M. S. Rotundo, C. Ginanneschi, I. Martellucci, E. Francini, et al.
Immunity Feedback and Clinical Outcome in Colon Cancer Patients Undergoing Chemoimmunotherapy with Gemcitabine + FOLFOX followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Aldesleukin (GOLFIG-1 Trial)
Clin. Cancer Res., July 1, 2008; 14(13): 4192 - 4199.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
T. Sittler, J. Zhou, J. Park, N. K. Yuen, S. Sarantopoulos, J. Mollick, R. Salgia, A. Giobbie-Hurder, G. Dranoff, and F. S. Hodi
Concerted Potent Humoral Immune Responses to Autoantigens Are Associated with Tumor Destruction and Favorable Clinical Outcomes without Autoimmunity
Clin. Cancer Res., June 15, 2008; 14(12): 3896 - 3905.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
F. S. Hodi, M. Butler, D. A. Oble, M. V. Seiden, F. G. Haluska, A. Kruse, S. MacRae, M. Nelson, C. Canning, I. Lowy, et al.
Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients
PNAS, February 26, 2008; 105(8): 3005 - 3010.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
X. Zang, R. H. Thompson, H. A. Al-Ahmadie, A. M. Serio, V. E. Reuter, J. A. Eastham, P. T. Scardino, P. Sharma, and J. P. Allison
B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome
PNAS, December 4, 2007; 104(49): 19458 - 19463.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
N. Cools, P. Ponsaerts, V. F. I. Van Tendeloo, and Z. N. Berneman
Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells
J. Leukoc. Biol., December 1, 2007; 82(6): 1365 - 1374.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
R. M. Wong, R. R. Scotland, R. L. Lau, C. Wang, A. J. Korman, W. M. Kast, and J. S. Weber
Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs
Int. Immunol., October 1, 2007; 19(10): 1223 - 1234.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
D. J. Powell Jr., A. Felipe-Silva, M. J. Merino, M. Ahmadzadeh, T. Allen, C. Levy, D. E. White, S. Mavroukakis, R. J. Kreitman, S. A. Rosenberg, et al.
Administration of a CD25-Directed Immunotoxin, LMB-2, to Patients with Metastatic Melanoma Induces a Selective Partial Reduction in Regulatory T Cells In Vivo
J. Immunol., October 1, 2007; 179(7): 4919 - 4928.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
F. S. Hodi
Cytotoxic T-Lymphocyte Associated Antigen-4
Clin. Cancer Res., September 15, 2007; 13(18): 5238 - 5242.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
G. Lizee, M. A. Cantu, and P. Hwu
Less Yin, More Yang: Confronting the Barriers to Cancer Immunotherapy
Clin. Cancer Res., September 15, 2007; 13(18): 5250 - 5255.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
X. Zang and J. P. Allison
The B7 Family and Cancer Therapy: Costimulation and Coinhibition
Clin. Cancer Res., September 15, 2007; 13(18): 5271 - 5279.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
J. Weber
Review: Anti CTLA-4 Antibody Ipilimumab: Case Studies of Clinical Response and Immune-Related Adverse Events
Oncologist, July 1, 2007; 12(7): 864 - 872.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
A. Ribas, D. C. Hanson, D. A. Noe, R. Millham, D. J. Guyot, S. H. Bernstein, P. C. Canniff, A. Sharma, and J. Gomez-Navarro
Tremelimumab (CP-675,206), a Cytotoxic T Lymphocyte Associated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer
Oncologist, July 1, 2007; 12(7): 873 - 883.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
E. MONTERO, L. ALONSO, R. PEREZ, and A. LAGE
Interleukin-2 Mastering Regulation in Cancer and Autoimmunity
Ann. N.Y. Acad. Sci., June 1, 2007; 1107(1): 239 - 250.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
E. M. Gabriel and E. C. Lattime
Anti-CTL-Associated Antigen 4: Are Regulatory T Cells a Target?
Clin. Cancer Res., February 1, 2007; 13(3): 785 - 788.
[Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
D. O'Mahony, J. C. Morris, C. Quinn, W. Gao, W. H. Wilson, B. Gause, S. Pittaluga, S. Neelapu, M. Brown, T. A. Fleisher, et al.
A Pilot Study of CTLA-4 Blockade after Cancer Vaccine Failure in Patients with Advanced Malignancy
Clin. Cancer Res., February 1, 2007; 13(3): 958 - 964.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. S. Ernstoff, T. S. Crocenzi, J. D. Seigne, N. A. Crosby, B. F. Cole, J. L. Fisher, J. C. Uhlenhake, D. Mellinger, C. Foster, C. J. Farnham, et al.
Developing a Rational Tumor Vaccine Therapy for Renal Cell Carcinoma: Immune Yin and Yang
Clin. Cancer Res., January 15, 2007; 13(2): 733s - 740s.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
G. Ferretti, A. Felici, M. S. Pino, and F. Cognetti
Does CTLA4 Influence the Suppressive Effect of CD25+CD4+ Regulatory T Cells?
J. Clin. Oncol., December 1, 2006; 24(34): 5469 - 5470.
[Full Text] [PDF]


Home page
BloodHome page
L. Gattinoni, A. Ranganathan, D. R. Surman, D. C. Palmer, P. A. Antony, M. R. Theoret, D. M. Heimann, S. A. Rosenberg, and N. P. Restifo
CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent
Blood, December 1, 2006; 108(12): 3818 - 3823.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
A. Hryniewicz, A. Boasso, Y. Edghill-Smith, M. Vaccari, D. Fuchs, D. Venzon, J. Nacsa, M. R. Betts, W.-P. Tsai, J.-M. Heraud, et al.
CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques
Blood, December 1, 2006; 108(12): 3834 - 3842.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
D. J. Powell Jr., M. E. Dudley, K. A. Hogan, J. R. Wunderlich, and S. A. Rosenberg
Adoptive Transfer of Vaccine-Induced Peripheral Blood Mononuclear Cells to Patients with Metastatic Melanoma following Lymphodepletion
J. Immunol., November 1, 2006; 177(9): 6527 - 6539.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
S. Read, R. Greenwald, A. Izcue, N. Robinson, D. Mandelbrot, L. Francisco, A. H. Sharpe, and F. Powrie
Blockade of CTLA-4 on CD4+CD25+ Regulatory T Cells Abrogates Their Function In Vivo
J. Immunol., October 1, 2006; 177(7): 4376 - 4383.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
C.-h. Lee, T. Kakinuma, J. Wang, H. Zhang, D. C. Palmer, N. P. Restifo, and S. T. Hwang
Sensitization of B16 tumor cells with a CXCR4 antagonist increases the efficacy of immunotherapy for established lung metastases.
Mol. Cancer Ther., October 1, 2006; 5(10): 2592 - 2599.
[Abstract] [Full Text] [PDF]


Home page
Genes Dev.Home page
L. Chin, L. A. Garraway, and D. E. Fisher
Malignant melanoma: genetics and therapeutics in the genomic era.
Genes & Dev., August 15, 2006; 20(16): 2149 - 2182.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
G. Lizee, L. G. Radvanyi, W. W. Overwijk, and P. Hwu
Improving Antitumor Immune Responses by Circumventing Immunoregulatory Cells and Mechanisms.
Clin. Cancer Res., August 15, 2006; 12(16): 4794 - 4803.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
K. E. Beck, J. A. Blansfield, K. Q. Tran, A. L. Feldman, M. S. Hughes, R. E. Royal, U. S. Kammula, S. L. Topalian, R. M. Sherry, D. Kleiner, et al.
Enterocolitis in Patients With Cancer After Antibody Blockade of Cytotoxic T-Lymphocyte-Associated Antigen 4
J. Clin. Oncol., May 20, 2006; 24(15): 2283 - 2289.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
C. P. Tarassoff, P. M. Arlen, and J. L. Gulley
Therapeutic vaccines for prostate cancer.
Oncologist, May 1, 2006; 11(5): 451 - 462.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
K. R. Lindsey, L. Gritz, R. Sherry, A. Abati, P. A. Fetsch, L. C. Goldfeder, M. I. Gonzales, K. A. Zinnack, L. Rogers-Freezer, L. Haworth, et al.
Evaluation of Prime/Boost Regimens Using Recombinant Poxvirus/Tyrosinase Vaccines for the Treatment of Patients with Metastatic Melanoma
Clin. Cancer Res., April 15, 2006; 12(8): 2526 - 2537.
[Abstract] [Full Text] [PDF]


Home page
Ann OncolHome page
S. Danson and P. Lorigan
Melanoma vaccines - they should work
Ann. Onc., April 1, 2006; 17(4): 539 - 541.
[Full Text] [PDF]


Home page
Arch DermatolHome page
S. H. Jaber, E. W. Cowen, L. R. Haworth, S. L. Booher, D. M. Berman, S. A. Rosenberg, and S. T. Hwang
Skin Reactions in a Subset of Patients With Stage IV Melanoma Treated With Anti-Cytotoxic T-Lymphocyte Antigen 4 Monoclonal Antibody as a Single Agent.
Arch Dermatol, February 1, 2006; 142(2): 166 - 172.
[Abstract] [Full Text] [PDF]


Home page
Ann. Surg. Oncol.Home page
A. V. Maker, G. Q. Phan, P. Attia, J. C. Yang, R. M. Sherry, S. L. Topalian, U. S. Kammula, R. E. Royal, L. R. Haworth, C. Levy, et al.
Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study
Ann. Surg. Oncol., December 1, 2005; 12(12): 1005 - 1016.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
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]


Home page
JCOHome page
M. S. Ernstoff
Self-Recognition and Tumor Response to Immunotherapy
J. Clin. Oncol., September 1, 2005; 23(25): 5875 - 5877.
[Full Text] [PDF]



About
JCO
 Editorial
Roster
 Advertising
Information
 Librarians &
Institutions
 Rights &
Permissions
 Site Map

Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online