IMMUNIZATION AGAINST A RAT COLON-CARCINOMA BY SODIUM BUTYRATE-TREATEDCELLS BUT NOT BY INTERLEUKIN 2-SECRETING CELLS

Background & Aims: Vaccination of patients with colon cancer with irra diated autologous tumor cells and bacille Calmette-Guerin (BCG) was re ported to augment mean survival. It was recently observed that a local treatment combining recombinant interleukin 2 and the differentiation agent sodium butyrate cured vats with colon cancer peritoneal carcino matosis. To optimize vaccination protocols, the comparison of the effi cacy of irradiated tumor cells mixed with BCG with that of interleukin 2-gene-transfected cells and of tumor cells pretreated with sodium bu tyrate was performed. Methods: The poorly immunogenic vat colon carcin oma cells PROb were used in a vaccination assay. Interleukin 2-transfe cted PROb cells, either proliferating or irradiated, weve used. The ef ficiency of irradiated PROb cells mixed with BCG, of interleukin 2-tra nsfected cells, or of cells pretreated with sodium butyrate was tested . Results: Vaccination with irradiated parental cells and BCG did not provide protection. Irradiated interleukin 2-transfected cells were po orly efficient in the vaccination assay. Conversely, vaccination with irradiated parental cells pretreated with sodium butyrate before injec tion provided good protection. Conclusions: Interleukin 2-secreting ce lls efficiently vaccinated animals when injected while replicating but not after irradiation. Conversely, sodium butyrate pretreatment provi ded a simple and efficient vaccination scheme that generated a long-te rm immune memory and allowed the use of irradiated cells.