This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Foon, K. A. Articles by Bhattacharya-Chatterjee, M. Search for Related Content PubMed PubMed Citation Articles by Foon, K. A. Articles by Bhattacharya-Chatterjee, M. Social Bookmarking                            What's this?

Clinical and Immune Responses in Advanced Melanoma Patients Immunized With an Anti-Idiotype Antibody Mimicking Disialoganglioside GD2

From the Division of Hematology/Oncology, Department of Internal Medicine, The Barrett Cancer Center for Prevention, Treatment and Research, University of Cincinnati College of Medicine and Oncology-Hematology Care, Inc, Cincinnati, OH; Mount Sinai Cancer Center, Miami, FL; Division of Hematology/Oncology, Department of Internal Medicine, and Lucille Parker Markey Cancer Center, University of Kentucky Medical Center, Lexington, KY; Division of Hematology/Oncology, Department of Internal Medicine, University of Arkansas School of Medicine, Little Rock, AK; Titan Pharmaceuticals, Inc, South San Francisco, CA; Aquila Biopharmaceuticals, Inc, Framingham, MA; and The Scripps Research Institute, La Jolla, CA.

Address reprint requests to Kenneth A. Foon, MD, Barrett Cancer Center, 234 Goodman St, ML 0502, Suite 1091, Cincinnati, OH 45219-2316; email kenneth.foon{at}uc.edu

PURPOSE: To determine immune responses and toxicity to the anti-idiotype vaccine, as well as clinical responses and survival, we initiated a clinical trial for patients with advanced melanoma treated with an anti-idiotype antibody (TriGem) that mimics the disialoganglioside GD2.

PATIENTS AND METHODS: Forty-seven patients with advanced melanoma received either 1-, 2-, 4-, or 8-mg doses of TriGem (Titan Pharmaceuticals Inc, South San Francisco, CA) mixed with QS-21 adjuvant (Aquila Biopharmaceuticals, Inc, Worcester, MA) 100 µg subcutaneously weekly for 4 weeks and then monthly until disease progression. Median age was 57 years, there were 32 men and 15 women, 43% of patients had undergone prior therapy for metastatic disease, 55% had disease confined to soft tissue, and 45% had visceral metastasis.

RESULTS: Hyperimmune sera from 40 of 47 patients showed an anti–anti-idiotype (Ab3) response. Patient Ab3 was truly Ab1' because it specifically bound purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody consisted of predominantly immunoglobulin (Ig)G, and all IgG subclasses were represented. One patient had a complete response that persisted at 24 months, and 12 patients were stable from 14+ to 37+ months (median, 18+ months). Disease progression occurred in 32 patients on study from 1 to 17 months (median, 5.5 months), and 21 have died at 1 to 16 months (median, 6 months). The Kaplan-Meier–derived overall median survival has not been reached. Median survival has not been reached for the 26 patients with soft tissue disease only and was 13 months for 21 patients with visceral metastasis. Toxicity consisted of local reaction at the site of injection and mild fever and chills.

CONCLUSION: TriGem has minimal toxicity and generates robust and specific IgG immune responses against GD2. Objective responses were minimal, but there may be a favorable impact on disease progression and survival that will require prospective randomized trials.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. M. Hernandez, D. Toledo, D. Martinez, T. Grinan, V. Brito, A. Macias, S. Alfonso, T. Rondon, E. Suarez, A. M. Vazquez, et al. Characterization of the Antibody Response against NeuGcGM3 Ganglioside Elicited in Non-Small Cell Lung Cancer Patients Immunized with an Anti-Idiotype Antibody J. Immunol., November 1, 2008; 181(9): 6625 - 6634. [Abstract] [Full Text] [PDF]

				S. Fest, N. Huebener, S. Weixler, M. Bleeke, Y. Zeng, A. Strandsby, R. Volkmer-Engert, C. Landgraf, G. Gaedicke, A. B. Riemer, et al. Characterization of GD2 Peptide Mimotope DNA Vaccines Effective against Spontaneous Neuroblastoma Metastases Cancer Res., November 1, 2006; 66(21): 10567 - 10575. [Abstract] [Full Text] [PDF]

				M. M. Uttenreuther-Fischer, J. A. Kruger, and P. Fischer Molecular Characterization of the Anti-Idiotypic Immune Response of a Relapse-Free Neuroblastoma Patient following Antibody Therapy: A Possible Vaccine against Tumors of Neuroectodermal Origin? J. Immunol., June 15, 2006; 176(12): 7775 - 7786. [Abstract] [Full Text] [PDF]

				G. Chong, A. Bhatnagar, D. Cunningham, T. M. Cosgriff, P. G. Harper, W. Steward, J. Bridgewater, M. Moore, J. Cassidy, R. Coleman, et al. Phase III trial of 5-fluorouracil and leucovorin plus either 3H1 anti-idiotype monoclonal antibody or placebo in patients with advanced colorectal cancer Ann. Onc., March 1, 2006; 17(3): 437 - 442. [Abstract] [Full Text] [PDF]

				X. Wang, E. C. Ko, L. Peng, S. D. Gillies, and S. Ferrone Human High Molecular Weight Melanoma-Associated Antigen Mimicry by Mouse Anti-Idiotypic Monoclonal Antibody MK2-23: Enhancement of Immunogenicity of Anti-Idiotypic Monoclonal Antibody MK2-23 by Fusion with Interleukin 2 Cancer Res., August 1, 2005; 65(15): 6976 - 6983. [Abstract] [Full Text] [PDF]

				C. Schwegler, A. Dorn-Beineke, S. Nittka, C. Stocking, and M. Neumaier Monoclonal Anti-idiotype Antibody 6G6.C4 Fused to GM-CSF Is Capable of Breaking Tolerance to Carcinoembryonic Antigen (CEA) in CEA-Transgenic Mice Cancer Res., March 1, 2005; 65(5): 1925 - 1933. [Abstract] [Full Text] [PDF]

				J. L. Murray, M. Gillogly, K. Kawano, C. L. Efferson, J. E. Lee, M. Ross, X. Wang, S. Ferrone, and C. G. Ioannides Fine Specificity of High Molecular Weight-Melanoma-Associated Antigen-Specific Cytotoxic T Lymphocytes Elicited by Anti-Idiotypic Monoclonal Antibodies in Patients with Melanoma Cancer Res., August 1, 2004; 64(15): 5481 - 5488. [Abstract] [Full Text] [PDF]

				S. Reinartz, S. Kohler, H. Schlebusch, K. Krista, P. Giffels, K. Renke, J. Huober, V. Mobus, R. Kreienberg, A. duBois, et al. Vaccination of Patients with Advanced Ovarian Carcinoma with the Anti-Idiotype ACA125: Immunological Response and Survival (Phase Ib/II) Clin. Cancer Res., March 1, 2004; 10(5): 1580 - 1587. [Abstract] [Full Text] [PDF]

				M. Lomas, W. Liauw, D. Packham, K. Williams, A. Kelleher, J. Zaunders, and R. Ward Phase I clinical trial of a human idiotypic p53 vaccine in patients with advanced malignancy Ann. Onc., February 1, 2004; 15(2): 324 - 329. [Abstract] [Full Text] [PDF]

				B. M. Bradt, S. J. DeNardo, G. R. Mirick, and G. L. DeNardo Documentation of Idiotypic Cascade after Lym-1 Radioimmunotherapy in a Patient with Non-Hodgkin's Lymphoma: Basis for Extended Survival? Clin. Cancer Res., September 1, 2003; 9(10): 4007S - 4012. [Abstract] [Full Text] [PDF]

				S. Reinartz, A. Hombach, S. Kohler, H. Schlebusch, D. Wallwiener, H. Abken, and U. Wagner Interleukin-6 Fused to an Anti-idiotype Antibody in a Vaccine Increases the Specific Humoral Immune Response against CA125+ (MUC-16) Ovarian Cancer Cancer Res., June 15, 2003; 63(12): 3234 - 3240. [Abstract] [Full Text] [PDF]

				K. A. Foon and M. Bhattacharya-Chatterjee Are Solid Tumor Anti-Idiotype Vaccines Ready for Prime Time?: Commentary re: U. Wagner et al., Immunological Consolidation of Ovarian Carcinoma Recurrences with Monoclonal Anti-Idiotype Antibody ACA125: Immune Responses and Survival in Palliative Treatment. Clin. Cancer Res., 7: 1154-1162, 2001. Clin. Cancer Res., May 1, 2001; 7(5): 1112 - 1115. [Full Text]