title: Phase I trial of a melanoma vaccine with gp100(280-288) peptide and tetanus helper peptide in adjuvant: immunologic and clinical outcomes.
abstract: A melanoma vaccine composed of HLA-A2-restricted peptide YLEPGPVTA (gp100(280)), with or without a modified T-helper epitope from tetanus toxoid AQYIKANSKFIGITEL, has been evaluated in a Phase I trial to assess safety and immunological response. The vaccines were administered s.c. in either of two adjuvants, Montanide ISA-51 or QS-21, to 22 patients with high-risk resected melanoma (stage IIB-IV). Local and systemic toxicities were mild and transient. We detected CTL responses to the gp100(280) peptide in peripheral blood in 14% of patients. Helper T-cell responses to the tetanus helper peptide were detected in 79% of patients and had a Th1 cytokine profile. One patient with a CTL response to gp100 had a recurrence in a lymph node 2 years later; her nodes contained CD8+ cells reactive to gp100(280) (0.24%), which proliferated in response to peptide. The overall survival of patients is 75% (95% confidence interval, 57-94%) at 4.7 years follow-up, which compares favorably with expected survival. Four of 14 patients who completed at least six vaccines subsequently developed metastases, all of which were solitary and surgically resectable. They remain alive and clinically free of disease at last follow-up. Data from this trial demonstrate immunogenicity of the gp100(280) peptide and suggest that immune responses may persist long-term in some patients. The frequency and magnitude of the CTL response may be improved with more aggressive vaccination regimens. Although this Phase I study was not intended to evaluate clinical benefit, the excellent survival of patients on this protocol suggests the possibility of a benefit that should be assessed in future studies.
authors.affiliation: Department of Surgery, University of Virginia, Charlottesville, 22908, USA. cls8h@virginia.edu
authors.forename: C L
authors.initials: CL
authors.lastname: Slingluff
authors.forename: G
authors.initials: G
authors.lastname: Yamshchikov
authors.forename: P
authors.initials: P
authors.lastname: Neese
authors.forename: H
authors.initials: H
authors.lastname: Galavotti
authors.forename: S
authors.initials: S
authors.lastname: Eastham
authors.forename: V H
authors.initials: VH
authors.lastname: Engelhard
authors.forename: D
authors.initials: D
authors.lastname: Kittlesen
authors.forename: D
authors.initials: D
authors.lastname: Deacon
authors.forename: S
authors.initials: S
authors.lastname: Hibbitts
authors.forename: W W
authors.initials: WW
authors.lastname: Grosh
authors.forename: G
authors.initials: G
authors.lastname: Petroni
authors.forename: R
authors.initials: R
authors.lastname: Cohen
authors.forename: C
authors.initials: C
authors.lastname: Wiernasz
authors.forename: J W
authors.initials: JW
authors.lastname: Patterson
authors.forename: B P
authors.initials: BP
authors.lastname: Conway
authors.forename: W G
authors.initials: WG
authors.lastname: Ross
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015789:HLA-A2 Antigen / Q000276:immunology; D006261:Headache / Q000139:chemically induced; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D009367:Neoplasm Staging; D010146:Pain / Q000139:chemically induced; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D010455:Peptides; D012503:Saponins / Q000008:administration & dosage / Q000009:adverse effects; D012867:Skin / Q000187:drug effects / Q000276:immunology; D012871:Skin Diseases / Q000139:chemically induced; D012882:Skin Tests; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D058951:gp100 Melanoma Antigen
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D010455:Peptides; D012503:Saponins; D013745:Tetanus Toxoid; D058951:gp100 Melanoma Antigen; C548641:gp100(280-288) melanoma antigen peptide; C078785:saponin QA-21V1; D007371:Interferon-gamma