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

• DOI: 10.1200/jco.2005.01.128
• Publication Date: 2004-12-22T03:00:17Z
• Authors: Kristin Sanderson; Ronald Scotland; Peter Lee; Dongxin Liu; Susan Groshen; Jolie Snively; Shirley Sian; Geoffrey Nichol; Thomas Davis; Tibor Keler; Michael Yellin; Jeffrey Weber
• Keywords: ELISPOT

Nineteen patients with high-risk resected stage III and IV melanoma were immunized three tumor antigen epitope peptides from gp100, MART-1, tyrosinase emulsified adjuvant Montanide ISA 51 received a fully human anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody MDX-010. Each of cohorts escalating doses vaccine primarily to evaluate the toxicities maximum-tolerated dose (MTD) MDX-010 vaccine. pharmacokinetics immune responses secondary end points.Peptide immunizations administered every 4 weeks for 6 months then 12 months. A leukapheresis obtain peripheral-blood mononuclear cells analyses was performed before treatment after sixth vaccination. Patients observed until relapse.Grade 3 gastrointestinal (GI) toxicity (diarrhea or abdominal pain) in highest cohort one middle who seemed be autoimmune. That defined MTD on this schedule at 1 mg/kg. Of eight evidence autoimmunity, have experienced disease relapse. 11 without autoimmune symptoms, nine Significant measured by tetramer enzyme-linked immunospot assays against gp100 MART-1.Dose-related adverse events, predominantly skin GI toxicities, reversible. mounted an antigen-specific response peptide when combined anti-CTLA-4 antibody.