title: Phase I study of a MUC1 vaccine composed of different doses of MUC1 peptide with SB-AS2 adjuvant in resected and locally advanced pancreatic cancer.
abstract: MUC1 is a glycoprotein overexpressed in tumors as a hypoglycosylated form. A vaccine composed of a 100-amino acid peptide corresponding to five 20-amino acid long repeats, and SB-AS2 adjuvant, was tested in a phase I study for safety, toxicity, and ability to elicit or boost MUC1-specific immune responses. Patients with resected or locally advanced pancreatic cancer without prior chemotherapy or radiotherapy were eligible. Escalating doses of the peptide (100, 300, 1,000, and 3,000 mug) were admixed with SB-AS2 and administered intramuscularly every 3 weeks for three doses, in cohorts of four patients. Sixteen patients were enrolled. Common adverse effects were grade 1 flu-like symptoms, tenderness, and erythema at the injection site. Delayed-type hypersensitivity (DTH) sites showed few or no T cells prevaccination (Pre V), but increased T-cell infiltration postvaccination (Post V). There was an increase in the percentage of CD8(+) T cells in the peripheral blood Post V. An increase in total MUC1-specific antibody was seen in some patients, and several patients developed IgG antibody. Two of 15 resected pancreatic cancer patients are alive and disease free at follow-up of 32 and 61 months. MUC1 100mer peptide with SB-AS2 adjuvant is a safe vaccine that induces low but detectable mucin-specific humoral and T-cell responses in some patients. No difference was seen between different peptide doses. Further evaluation is warranted to examine the effect on disease-free survival and overall survival, especially in early disease and in the absence of immunosuppressive standard therapy.
authors.affiliation: UPMC Cancer Pavilion, University of Pittsburgh Cancer Institute, 5150 Centre Avenue, #562, Pittsburgh, PA 15232, USA.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Lee
authors.forename: John
authors.initials: J
authors.lastname: McKolanis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hitbold
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schraut
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moser
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Warnick
authors.forename: Theresa
authors.initials: T
authors.lastname: Whiteside
authors.forename: Jennifer
authors.initials: J
authors.lastname: Osborne
authors.forename: Hyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Roger
authors.initials: R
authors.lastname: Day
authors.forename: Monica
authors.initials: M
authors.lastname: Troetschel
authors.forename: Olivera J
authors.initials: OJ
authors.lastname: Finn
mesh_terms: D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000737:chemistry; D006509:Hepatitis B / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed; D007107:Immune System; D007074:Immunoglobulin G / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D010455:Peptides / Q000737:chemistry; D018714:Radiotherapy, Adjuvant; D012503:Saponins / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D006023:Glycoproteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008050:Lipid A; D018396:Mucin-1; D010455:Peptides; D012503:Saponins; C472719:adjuvant SBAS-2