| The SASK mouse model, which utilizes the LM-1 cell line, is one of the few syngeneic models for epithelial ovarian cancer. We used a serological method, serological identification of antigens by recombinant expression cloning (SEREX), to identify murine ovarian-tumor antigens in this model. Animals were immunized with the LM-1 cell line and challenged to verify that the LM-1 cells were immunogenic. The antiserum was used to screen an LM-1 cDNA library. Seven reactive clones were isolated and characterized, including the ribosomal protein S2, cyclin I and β′COP. The ribosomal protein is a known tumor antigen highly expressed in the human ovarian tumor cell line, PA-1. Cyclin I is a cell-cycle-regulatory protein and may play a role in ovarian tumorigenesis. The human homologue of β ′COP, a vesicular trafficking protein, was previously identified in our laboratory as a candidate tumor antigen. Because β′ COP is immunogenic in the SASK mouse, human ovarian-cancer-patient sera were tested for reactivity with this protein. We found that 33 of 42 (78.6%) sera from patients had antibodies that were reactive to β ′COP, whereas only 1 of 48 serum samples from healthy controls had detectable antibodies to this protein. This suggests that tumor antigens identified in the SASK mouse can lead to the identification of relevant human homologues, which may be useful as markers or novel targets for immunotherapy.; To determine whether these proteins act as tumor-rejection antigens, mice were immunized with plasmid DNA encoding these newly identified tumor antigens. Upon challenge, the immunized animals showed delayed tumor growth, suggesting that an effective antitumor immune response could be elicited.; Our studies show that SEREX can be used to identify murine tumor associated antigens (TAAs) in the SASK model, in addition to human homologues that are implicated inhuman cancers. Thus, the SASK mouse may be a good immunotherapy model for preclinical studies. Finally, characterization of these antigens may lead to the development of improved screening methods, novel treatment strategies, and a better understanding of ovarian cancer biology. |
