Induction of IgG subclass responses in colorectal carcinoma patients vaccinated with recombinant carcinoembryonic antigen

There is scanty information on the IgG subclass response after vaccination against cancer antigens. The induction and development of the IgG subclass responses in 18 colorectal carcinoma patients vaccinated s.c. seven times with recombinant human carcinoembryonic antigen (rhCEA) over a 12-month period were analyzed by ELISA. The patients were followed for 3 years. Four rhCEA doses were used, and half of the patients also received granulocyte macrophage-colony stimulating factor (GM-CSF) as an adjuvant. Anti-rhCEA-specific IgG1 and IgG4 responses and, to a lesser degree, IgG2 responses were markedly enhanced by concomitant GM-CSF administration, whereas the antigen dose was of minor importance. Almost no IgG3 response was observed. A significant antibody response was noted within the first weeks for IgG1 and IgG2 but noted several months later for IgG4. The responses gradually increased by repeated immunizations and peaked around 12 months for IgG1 and a few months later for IgG2 and IgG4. A sustained but reduced response was noted for these three subclasses at 24 and 36 months. Interestingly, there was a gradual shift from a predominant IgG1 response at 6 months to an IgG4 response at 15 months. No significant change in total concentrations of the four IgG subclasses was observed comparing prevaccination concentrations with concentrations at 12 months, indicating an antigen-specific effect of GM-CSF administration on the anti-rhCEA response. The clinical significance of the individual IgG subclass antibodies for tumor response is not clear and requires additional studies.