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Immunization WithMutantp53-andK-ras–DerivedPeptides in CancerPatients: ImmuneResponse and ClinicalOutcome David P. CarboneI. Frank CiernikMichael J. Kelley2005 год

Immunization With Mutantp53- andK-ras–Derived Peptides in Cancer Patients: Immune Response and Clinical Outcome
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Аннотация: To determine the ability to induce tumor-specific immunity with individual mutant K-ras-or p53-derived peptides and to monitor clinical outcome.Patients in varying stages of disease underwent genetic analysis for mutations in K-ras and p53. Thirty-nine patients were enrolled. Seventeen-mer peptides were custom synthesized to the corresponding mutation. Baseline immunity was assessed for cytotoxic T-lymphocyte (CTL) response and interferon gamma (IFN-gamma) release from mutant peptide-primed lymphocytes. Patients' peripheral-blood mononuclear cells were pulsed with the corresponding peptide, irradiated, and applied intravenously. Patients were observed for CTL, IFN-gamma, interleukin (IL) -2, IL-5, and granulocyte-macrophage colony-stimulating factor responses, for treatment-related toxicity, and for tumor response.No toxicity was observed. Ten (26%) of 38 patients had detectable CTL against mutant p53 or K-ras, and two patients were positive for CTL at baseline. Positive IFN-gamma responses occurred in 16 patients (42%) after vaccination, whereas four patients had positive IFN-gamma reaction before vaccination. Of 29 patients with evident disease, five experienced a period of stable disease. Favorable prognostic markers were detectable CTL activity and a positive IFN-gamma reaction but not IL-5 release. Median survival times of 393 v 98 days for a positive versus negative CTL response (P = .04), respectively, and of 470 v 88 days for a positive versus negative IFN-gamma response (P = .02), respectively, were detected.Custom-made peptide vaccination is feasible without any toxicity. CTL and cytokine responses specific to a given mutation can be induced or enhanced with peptide vaccines. Cellular immunity to mutant p53 and K-ras oncopeptides is associated with longer survival.
Год издания: 2005
Авторы: David P. Carbone, I. Frank Ciernik, Michael J. Kelley, Malcolm C. Smith, Sorena Nadaf, Denise Kavanaugh, V. Ellen Maher, Michael Stipanov, David Contois, Bruce E. Johnson, C D Pendleton, Burkhardt Seifert, Charley Carter, Elizabeth J. Read, Jay J. Greenblatt, Lois E. Top, Morris I. Kelsey, John D. Minna, Jay A. Berzofsky
Издательство: Lippincott Williams & Wilkins
Источник: Journal of Clinical Oncology
Ключевые слова: Immunotherapy and Immune Responses, Cancer Immunotherapy and Biomarkers, vaccines and immunoinformatics approaches
Другие ссылки: Journal of Clinical Oncology (PDF)
Journal of Clinical Oncology (HTML)
Zurich Open Repository and Archive (University of Zurich) (HTML)
PubMed (HTML)