title: Durable carcinoembryonic antigen (CEA)-specific humoral and cellular immune responses in colorectal carcinoma patients vaccinated with recombinant CEA and granulocyte/macrophage colony-stimulating factor.
abstract: Previous studies have indicated that carcinoembryonic antigen (CEA) might be a suitable immunotherapeutic target in colorectal carcinoma (CRC). The aim of the present study was to analyze the immunological and clinical effects of vaccination with CEA together with the adjuvant granulocyte/macrophage colony-stimulating factor (GM-CSF).
  
  
  
  Twenty-four resected CRC patients without macroscopic disease were immunized seven times with recombinant CEA at four different dose levels over a 12-month period. Half of the patients received GM-CSF (80 microg/day for 4 consecutive days) at each immunization. Patients were monitored immunologically for 36 months and clinically for 76 months. T-cell response was evaluated by a [(3)H]thymidine incorporation assay, and IgG response was determined by ELISA.
  
  
  
  Minor local side effects were common. All 12 patients (100%) in the GM-CSF group developed a CEA-specific T-cell as well as an IgG response. The corresponding figures in the CEA alone group were 9 of 12 (75%) and 8 of 12 (66%), respectively. GM-CSF significantly augmented the amplitude of the T-cell response and the IgG titers. No dose-response relationship was noted. The immune responses at 12 months persisted 24 months after the last vaccination. Anti-CEA IgG titers were associated with increased survival (P < 0.05), whereas standard prognostic factors had no relationship, with the exception of serum CEA value.
  
  
  
  Vaccination with recombinant CEA and GM-CSF appears to be a nontoxic regimen inducing potent and durable antigen-specific IgG and T-cell response. The results of this study justify more extensive trials with recombinant CEA protein for immunotherapy of CRC.
authors.affiliation: Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Ullenhag
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Frödin
authors.forename: Mahmood
authors.initials: M
authors.lastname: Jeddi-Tehrani
authors.affiliation: Department of Oncology and Cancer Centre Karolinska, Karolinska Hospital, Stockholm, Sweden
authors.forename: Niklas
authors.initials: N
authors.lastname: Lidströmer
authors.forename: Karin
authors.initials: K
authors.lastname: Strigård
authors.forename: Emma
authors.initials: E
authors.lastname: Eriksson
authors.forename: Ali
authors.initials: A
authors.lastname: Samanci
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Choudhury
authors.forename: Bo
authors.initials: B
authors.lastname: Nilsson
authors.forename: Eva D
authors.initials: ED
authors.lastname: Rossmann
authors.forename: Szilvia
authors.initials: S
authors.lastname: Mosolits
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000737:chemistry; D019496:Cancer Vaccines / Q000737:chemistry; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins / Q000737:chemistry; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor