title: Induction of IgM, IgA and IgE antibodies in colorectal cancer patients vaccinated with a recombinant CEA protein.
abstract: OBJECTIVE
  Previous clinical studies have indicated that natural IgM antibodies have the ability to induce apoptosis of tumor cells but IgE and IgA may also mediate tumor cell killing (in addition to IgG). The aim of the study was to analyse induction of IgM, IgA and IgE antibodies in patients vaccinated with the tumor associated antigen CEA.
  
  
  METHODS
  Twenty-four resected CRC patients without macroscopic disease were immunized seven times with CEA ± GM-CSF. Four different dose schedules were used over a 12-month period. IgM, IgA and IgE antibody responses against recombinant CEA were determined by ELISA. Patients were monitored immunologically for 36 months and clinically for 147 months.
  
  
  RESULTS
  GM-CSF significantly augmented the anti-CEA response for all three antibody classes. Low dose of CEA tended to induce a higher IgM, IgA or IgE anti-CEA antibody response than higher. Anti-CEA IgA antibodies could lyse CEA positive tumor cells in antibody dependent cellular cytotoxicity (ADCC) as well as in complement dependent cytotoxicity (CDC). A significant correlation between survival and high IgA anti-CEA titers was noted (p = 0.02) irrespective of GM-CSF treatment.
  
  
  CONCLUSIONS
  The observation that IgA anti-CEA antibodies were cytotoxic and associated with improved survival might indicate that also these antibodies may exert a clinical anti-tumor effect.
authors.affiliation: Department of Oncology and CancerCentreKarolinska at the Karolinska Institute, Karolinska University Hospital Solna, SE-171 76, Stockholm, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Staff
authors.forename: Carl G M
authors.initials: CG
authors.lastname: Magnusson
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hojjat-Farsangi
authors.forename: Szilvia
authors.initials: S
authors.lastname: Mosolits
authors.forename: Maria
authors.initials: M
authors.lastname: Liljefors
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Frödin
authors.forename: Britta
authors.initials: B
authors.lastname: Wahrén
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Ullenhag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000920:Antibody-Dependent Cell Cytotoxicity; D017209:Apoptosis; D019496:Cancer Vaccines / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C082430:molgramostim