title: Safety and immunogenicity of a human and mouse gp100 DNA vaccine in a phase I trial of patients with melanoma.
abstract: A differentiation antigen commonly expressed on melanoma cells, gp100 is the target of infiltrating T cells. We conducted a phase I randomized cross-over trial of melanoma patients with either xenogeneic (mouse) or human gp100 plasmid DNA injected intramuscularly at three dosages (100, 500 or 1,500 microg) every three weeks for three doses. After the first three injections, patients were then immunized three times with gp100 from the other species. Peripheral blood samples were analyzed at various time points following 10-day culture with gp100 peptides using multi-parametric flow cytometry. A total of 19 patients were enrolled, with 18 assessable for immune function and survival. 14 (74%) were male, with a median age of 56 years (range, 20-82). All patients had no evidence of disease; 10 (53%) had stage III disease, 3 each (16%) had stage IIB and IV disease, 2 (11%) had choroidal and 1 (5%) had anal mucosal involvement. With a median follow-up of 30 months, median progression-free survival (PFS) is 44 months. Median survival is not reached. There was no grade 3/4 toxicity; the most common grade 1/2 toxicity was an injection site reaction in 12 patients (63%, all grade 1). Five patients developed CD8+ cells binding gp100(280-288) HLA-A2-restricted tetramer. One patient had an increase in CD8+ IFN-gamma+ cells. This xenogeneic immunization strategy was safe and associated with minimal toxicity. There was also evidence of immune response.
authors.affiliation: Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering Institute, New York, NY, USA.
authors.forename: Jianda
authors.initials: J
authors.lastname: Yuan
authors.forename: Geoffrey Y
authors.initials: GY
authors.lastname: Ku
authors.forename: Humilidad F
authors.initials: HF
authors.lastname: Gallardo
authors.forename: Francesca
authors.initials: F
authors.lastname: Orlandi
authors.forename: Gregor
authors.initials: G
authors.lastname: Manukian
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Rasalan
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Shachi
authors.initials: S
authors.lastname: Vyas
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Mu
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
authors.forename: Susan E
authors.initials: SE
authors.lastname: Krown
authors.forename: Katherine
authors.initials: K
authors.lastname: Panageas
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Terzulli
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Alan N
authors.initials: AN
authors.lastname: Houghton
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D015789:HLA-A2 Antigen; D006801:Humans; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D010446:Peptide Fragments; D010455:Peptides; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D010455:Peptides; C548642:Pmel protein, mouse; D019444:Vaccines, DNA; D058951:gp100 Melanoma Antigen; C548641:gp100(280-288) melanoma antigen peptide