title: Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer.
abstract: OBJECTIVE
  The tumor-associated self-antigen p53 is commonly overexpressed in cancer, including colorectal cancer, and can serve as a target for immunotherapy. The safety and immunogenicity of a p53 synthetic long peptide (p53-SLP) vaccine were investigated in patients treated for metastatic colorectal cancer.
  
  
  METHODS
  Ten patients were vaccinated twice with a set of 10 overlapping p53-SLP in a phase I/II trial. Both the safety and the breadth, magnitude, and polarization of vaccine-induced p53-specific T cells was evaluated in blood samples drawn before and after vaccination by IFN-gamma enzyme-linked immunospot, proliferation, cytokine secretion, and multiparameter flow cytometry. The migratory capacity of p53-specific T cells was evaluated by assessing their presence in a biopsy of the second vaccination site.
  
  
  RESULTS
  Toxicity was limited to grade 1/2, mostly at the vaccination site. p53-specific T-cell responses were induced in 9 of 10 colorectal cancer patients as measured by IFN-gamma enzyme-linked immunospot, proliferation, and cytokine bead array. In 6 of 9 tested patients, p53-specific T-cell reactivity persisted at least 6 months. Furthermore, p53-specific T cells isolated from the vaccination site were characterized as CD4+ T cells producing both T-helper types 1 and 2 cytokines on stimulation with p53 peptide and p53 protein. Multiparameter flow cytometry revealed that only a minor population of the p53-specific CD4+ T cells was optimally polarized.
  
  
  CONCLUSIONS
  The p53-SLP vaccine is safe and capable to induce p53-specific T-cell responses in patients treated for colorectal cancer. New trials should focus on improving the polarization of the p53-SLP vaccine-induced T-cell response.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Speetjens
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.forename: Farah
authors.initials: F
authors.lastname: Essahsah
authors.forename: Anne Marie E G
authors.initials: AM
authors.lastname: Voet van den Brink
authors.forename: M Graziella Kallenberg
authors.initials: MG
authors.lastname: Lantrua
authors.forename: A Rob P M
authors.initials: AR
authors.lastname: Valentijn
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostendorp
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Fathers
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D016159:Tumor Suppressor Protein p53; D022223:Vaccines, Subunit; C000609547:p53 synthetic long peptide vaccine