Immunization with mutant p53- and K-ras-derived peptides in cancer patients: Immune response and clinical outcome

David P. Carbone, I. Frank Ciernik, Michael J. Kelley, M. Charles Smith, Sorena Nadaf, Denise Kavanaugh, V. Ellen Maher, Michael Stipanov, David Contois, Bruce E. Johnson, C. David Pendleton, Burkhardt Seifert, Charley Carter, Elizabeth J. Read, Jay Greenblatt, Lois E. Top, Morris I. Kelsey, John D. Minna, Jay A. Berzofsky

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Purpose: To determine the ability to induce tumor-specific immunity with individual mutant K-ras- or p53-derived peptides and to monitor clinical outcome. Patients and Methods: 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-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. Results: 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-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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)5099-5107
Number of pages9
JournalJournal of Clinical Oncology
Volume23
Issue number22
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Carbone, D. P., Ciernik, I. F., Kelley, M. J., Smith, M. C., Nadaf, S., Kavanaugh, D., Maher, V. E., Stipanov, M., Contois, D., Johnson, B. E., Pendleton, C. D., Seifert, B., Carter, C., Read, E. J., Greenblatt, J., Top, L. E., Kelsey, M. I., Minna, J. D., & Berzofsky, J. A. (2005). Immunization with mutant p53- and K-ras-derived peptides in cancer patients: Immune response and clinical outcome. Journal of Clinical Oncology, 23(22), 5099-5107. https://doi.org/10.1200/JCO.2005.03.158