title: Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers.
abstract: BACKGROUND
  There is mounting evidence describing the immunosuppressive role of bulky metastatic disease, thus countering the therapeutic effects of tumor vaccine. Therefore, adjuvant immunotherapy may have a better impact on clinical outcome. In this phase II clinical trial, we aimed to test the feasibility of using a specific mutant ras peptide vaccine as an adjuvant immunotherapy in pancreatic and colorectal cancer patients.
  
  
  METHODS
  Twelve patients with no evidence of disease (NED), five pancreatic and seven colorectal cancer patients were vaccinated subcutaneously with 13-mer mutant ras peptide, corresponding to their tumor's ras mutation. Vaccinations were given every 4 weeks, up to a total of six vaccines.
  
  
  RESULTS
  No serious acute or delayed systemic side effects were seen. We detected specific immune responses to the relevant mutant ras peptide by measuring IFN-gamma mRNA expression by quantitative real-time PCR. Five out of eleven patients showed a positive immune response. Furthermore, the five pancreatic cancer patients have shown a mean disease-free survival (DFS) of 35.2+ months and a mean overall survival (OS) of 44.4+ months. The seven colorectal cancer patients have shown a mean disease-free survival (DFS) of 27.2+ months and a mean overall survival (OS) of 41.5+ months.
  
  
  CONCLUSIONS
  In this study, we found that it is feasible to use mutant ras vaccine in the adjuvant setting. This vaccine is safe, can induce specific immune responses, and it appears to have a positive outcome in overall survival. Therefore, we believe that such an approach warrants further investigation in combination with other therapies.
authors.affiliation: Cancer Vaccine Section, Vaccine Branch, NCI, NIH, NNMC, Bldg 8, Room 5101, 8901 Wisconsin Ave, Bethesda, MD 20889, USA.
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Moujahed
authors.initials: M
authors.lastname: Achtar
authors.forename: Maurizio
authors.initials: M
authors.lastname: Provenzano
authors.forename: Vincent E
authors.initials: VE
authors.lastname: Herrin
authors.forename: Robert
authors.initials: R
authors.lastname: Behrens
authors.forename: Michael
authors.initials: M
authors.lastname: Hamilton
authors.forename: Sarah
authors.initials: S
authors.lastname: Bernstein
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Barry
authors.initials: B
authors.lastname: Gause
authors.forename: Francesco
authors.initials: F
authors.lastname: Marincola
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D011905:Genes, ras; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D010865:Pilot Projects
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines