Immunization With Mutantp53- andK-ras–Derived Peptides in Cancer Patients: Immune Response and Clinical Outcome
| Autor: | Michael Stipanov, Jay A. Berzofsky, M. Charles Smith, I. Frank Ciernik, Denise Kavanaugh, Charley Carter, Elizabeth J. Read, David Contois, Morris I. Kelsey, Sorena Nadaf, Burkhardt Seifert, Lois E. Top, John D. Minna, C. David Pendleton, Bruce E. Johnson, Michael J. Kelley, David P. Carbone, Jay Greenblatt, V. Ellen Maher |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Cancer Research Mutant Cancer Vaccines Peripheral blood mononuclear cell Interferon-gamma Immune system Immunity Neoplasms Humans Medicine Cytotoxic T cell Interferon gamma Aged business.industry Interleukin Middle Aged Genes p53 Prognosis Survival Analysis CTL Genes ras Treatment Outcome Oncology Immunology Cancer research Cytokines Female Tumor Suppressor Protein p53 business T-Lymphocytes Cytotoxic medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 23:5099-5107 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2005.03.158 |
| Popis: | PurposeTo determine the ability to induce tumor-specific immunity with individual mutant K-ras–or p53-derived peptides and to monitor clinical outcome.Patients and MethodsPatients 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-γ) 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-γ, interleukin (IL) -2, IL-5, and granulocyte-macrophage colony-stimulating factor responses, for treatment-related toxicity, and for tumor response.ResultsNo 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-γ responses occurred in 16 patients (42%) after vaccination, whereas four patients had positive IFN-γ 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-γ 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-γ response (P = .02), respectively, were detected.ConclusionCustom-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. |
| Databáze: | OpenAIRE |
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