title: Induction of p53-specific immune responses in colorectal cancer patients receiving a recombinant ALVAC-p53 candidate vaccine.
abstract: OBJECTIVE
  The tumor-associated auto-antigen p53 is commonly overexpressed in various types of human cancer, including colorectal cancer. Experiments in preclinical models have shown that it can serve as a target for T-cell-mediated tumor-eradication. The feasibility of a p53-specific therapeutic vaccination was investigated in cancer patients.
  
  
  METHODS
  A Phase I/II dose-escalation study was performed that evaluated the effect of a recombinant canarypoxvirus (ALVAC) vaccine encoding wild-type human p53 in 15 patients with advanced colorectal cancer. Each group of five patients received three i.v. doses of one-tenth of a dose, one-third of a dose, or 1 dose of the vaccine [1 dose = 1 x 10(7.5) cell culture infectious dosis (CCID)50].
  
  
  RESULTS
  Potent T-cell and IgG antibody responses against the vector component of the ALVAC vaccine were induced in the majority of the patients. Enzyme-linked immunosorbent-spot assay (ELISPOT) analysis of vaccine-induced immunity revealed the presence of IFN-gamma-secreting T cells against both ALVAC and p53, whereas no significant interleukin-4 responses were detected. Vaccine-mediated enhancement of p53-specific T-cell immunity was found in two patients in the highest-vaccine-dose group.
  
  
  CONCLUSIONS
  This study demonstrated the feasibility, even in patients with advanced cancer, to elicit immune responses against the ubiquitously expressed tumor-associated auto-antigen p53. Our results form the basis for additional studies that will explore the antitumor capacity of p53 containing multivalent vaccines in cancer patients with limited tumor burden.
authors: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, the Netherlands. shvdburg@worldonline.nl
authors: Sjoerd H
authors: SH
authors: van der Burg
authors: Anand G
authors: AG
authors: Menon
authors: Anke
authors: A
authors: Redeker
authors: Marie-Claude
authors: MC
authors: Bonnet
authors: Jan Wouter
authors: JW
authors: Drijfhout
authors: Rob A E M
authors: RA
authors: Tollenaar
authors: Cornelis J H
authors: CJ
authors: van de Velde
authors: Philippe
authors: P
authors: Moingeon
authors: Peter J K
authors: PJ
authors: Kuppen
authors: Rienk
authors: R
authors: Offringa
authors: Cornelis J M
authors: CJ
authors: Melief
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation; D028121:Canarypox virus / Q000235:genetics; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007075:Immunoglobulin M / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53