title: An open-label, prospective phase I/II study evaluating the immunogenicity and safety of a ras peptide vaccine plus GM-CSF in patients with non-small cell lung cancer.
abstract: Mutations of the ras gene have been reported in 20-40% of NSCLC patients. If present, they are critical for the malignant phenotype of these tumors. Therefore, targeting them by specific vaccination is a promising therapeutic approach. In a clinical trial we screened for ras mutations in patients with NSCLC. Patients with ras-positive tumors were immunized six times intradermally with a mixture of seven peptides representing the most common ras mutations. Objectives of the study were the feasibility, efficacy and safety of the vaccination. In addition, the induction of a specific immune reaction was investigated by DTH tests, and the induction of peptide-specific T cells was tested in ex vivo IFN-gamma-ELISPOT assays. Five of 18 patients had ras mutations at codon 12. Four of these patients, all with adenocarcinomas (stage I: n=3, stage IV: n=1) entered the study. The patient with stage IV disease withdrew prematurely after the third application because of disease progression associated with pulmonary embolism. Ras-specific T cells were not detected ex vivo. However, one patient developed a positive DTH reaction after the fifth vaccination that increased after the sixth vaccination. Our results are in line with earlier trials reporting ras mutations in 20-40% of NSCLC patients. Vaccination with mutated ras peptides is feasible and well tolerated. One patient revealed a positive DTH test. An ex vivo detectable T cell response was not induced in any of the patients.
authors.affiliation: III. Medical Department, Mainz University Hospital, Langenbeckstrasse 1, 55101 Mainz, Germany.
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Meyer
authors.forename: Stephanie
authors.initials: S
authors.lastname: Korn
authors.forename: Patrick
authors.initials: P
authors.lastname: Micke
authors.forename: Kai
authors.initials: K
authors.lastname: Becker
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.forename: Thomas
authors.initials: T
authors.lastname: Wölfel
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
mesh_terms: D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D003062:Codon; D003131:Combined Modality Therapy / Q000009:adverse effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D018631:ras Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D003062:Codon; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018631:ras Proteins