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Originally published as JCO Early Release 10.1200/JCO.2005.01.128 on December 21 2004

Journal of Clinical Oncology, Vol 23, No 4 (February 1), 2005: pp. 741-750
© 2005 American Society of Clinical Oncology.
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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

Kristin Sanderson, Ronald Scotland, Peter Lee, Dongxin Liu, Susan Groshen, Jolie Snively, Shirley Sian, Geoffrey Nichol, Thomas Davis, Tibor Keler, Michael Yellin, Jeffrey Weber

From the Departments of Medicine, Urology, and Preventive Medicine, Keck/University of Southern California School of Medicine, Los Angeles; Department of Medicine, Stanford University School of Medicine, Stanford, CA; and Medarex Inc, Bloomsbury, NJ

Address reprint requests to Jeffrey Weber, MD, PhD, Department of Medicine, Keck School of Medicine, University of Southern California/Norris Cancer Center, 1441 Eastlake Ave, Los Angeles, CA 90033; e-mail: jweber{at}usc.edu

PURPOSE: Nineteen patients with high-risk resected stage III and IV melanoma were immunized with three tumor antigen epitope peptides from gp100, MART-1, and tyrosinase emulsified with adjuvant Montanide ISA 51 and received a fully human anti-cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) monoclonal antibody MDX-010. Each of three cohorts received escalating doses of antibody with vaccine primarily to evaluate the toxicities and maximum-tolerated dose (MTD) of MDX-010 with vaccine. MDX-010 pharmacokinetics and immune responses were secondary end points.

PATIENTS AND METHODS: Peptide immunizations with MDX-010 were administered every 4 weeks for 6 months and then every 12 weeks for 6 months. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was performed before treatment and after the sixth vaccination. Patients were observed until relapse.

RESULTS: Grade 3 gastrointestinal (GI) toxicity (diarrhea or abdominal pain) was observed in three patients in the highest dose cohort and one in the middle dose cohort who seemed to be autoimmune. That defined the MTD with vaccine on this schedule at 1 mg/kg. Of eight patients with evidence of autoimmunity, three have experienced disease relapse. Of 11 patients without autoimmune symptoms, nine have experienced disease relapse. Significant immune responses were measured by tetramer and enzyme-linked immunospot assays against gp100 and MART-1.

CONCLUSION: Dose-related autoimmune adverse events, predominantly skin and GI toxicities, were reversible. Patients mounted an antigen-specific immune response to a peptide vaccine when combined with a human anti–CTLA-4 antibody.

Supported by a grant from the Food and Drug Administration's Orphan Drug Program (FD-001-01) and by a grant from Medarex Corp.

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


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[Abstract] [Full Text] [PDF]

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Home page
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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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Arch Dermatol, February 1, 2006; 142(2): 166 - 172.
[Abstract] [Full Text] [PDF]

Home page
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[Full Text] [PDF]

Home page
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Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Abstract] [Full Text] [PDF]

Home page
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[Full Text] [PDF]

Home page
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Home page
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[Abstract] [Full Text] [PDF]

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