THE DEVELOPMENT OF A NOVEL IMMUNOTHERAPY MODEL OF HUMAN OVARIAN-CANCER IN HUMAN PBL-SEVERE COMBINED IMMUNODEFICIENT (SCID) MICE

The reported ability of SCID mice to accept xenografts of both human t umours and peripheral blood lymphocytes (PBL) provides the potential f or the development of novel immunotherapy models in these animals. Thi s study describes the development of a novel small animal model of hum an ovarian cancer. This was achieved by engrafting a human ovarian can cer cell line (Ovan-4) into the peritoneal cavity of immunodeficient S CID and immune reconstituted human PBL-SCID mice. When transplanted to SCID mice this cell line exhibited growth characteristics similar to the clinical disease observed in patients with implantation of metasta tic nodules onto the interior surface of the peritoneal wall. Reconsti tuted human PBL-SCID mice challenged with identical numbers of Ovan-4 cells exhibited a significant increase in survival time. suggesting a role for cells of the human immune system in preventing the developmen t of this type of malignancy ht vivo. Furthermore, vaccination of huma n PBL-SCID mice against Ovan-4 produced tumour-specific human antibodi es in the serum of these animals. Animals reconstituted with CD8-deple ted PBL exhibited increased serum immunoglobulin levels and produced e nhanced anti-Ovan-4 activity after vaccination. Subsequent challenge o f these animals with Ovan-4 revealed a further increase in survival ti me. These results suggest that human antibodies may have a role in imm unity against ovarian cancer and could be of therapeutic value in this type of disease.