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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. (Botling)
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2007 (English)In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 58, no 1, 88-94 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2007. Vol. 58, no 1, 88-94 p.
Keyword [en]
Immunogenicity, Non-small cell lung cancer, Ras gene, Ras mutation, Ras peptide vaccination, Vaccination
National Category
Medical and Health Sciences
Research subject
Lung Medicine; Pathology
URN: urn:nbn:se:uu:diva-125841DOI: 10.1016/j.lungcan.2007.05.003ISI: 000250248600013PubMedID: 17599645OAI: oai:DiVA.org:uu-125841DiVA: diva2:321078
Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2011-01-20Bibliographically approved

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