Modulation of the rat tumor-associated shedding antigen (CE7) and augmentation of immunogenicity by irradiation

We have previously reported that rat fibrosarcoma KMT-17 cells and their in vitro counterparts, cloned A3 cells, shed a tumor-associated antigen (TAA), termed CE7, from the cell surface on vesicular membranes, under growth-enhancing conditions. This study shows that irradiation (1 approximately Gy) from a 60Co source, inhibited A3 cell growth dose-dependently and correspondingly increased CE7 expression by A3 cells as determined by anti-CE7 monoclonal antibody using flow cytometry. CE7 expression gradually increased with increasing doses of irradiation and reached a peak level at 30Gy. After 30Gy irradiation, CE7 expressing A3 cells were fixed with 1% paraformaldehyde and were used to intradermally immunize syngenic rats. Immunized rats developed transplantation resistance to the parent KMT-17 cells as compared to rats immunized with unirradiated A3 cells. Rat MHC class 1 antigen expression was slightly decreased by irradiation and therefore, resistance to tumor transplantation appeared to arise solely due to the enhancing effects of irradiation on TAA expression which increases the antigenicity of the tumor cells coverting them to an effective stimulator of antitumor effector cells. This phenomenon may offer a possibility of the resistance to the re-emergence and metastasis of the tumor like a KMT-17 through the induction of antitumor memory cells.