The development of a novel immunotherapy model of human ovarian cancer in human PBL-severe combined immunodeficient (SCID) mice

Abstract

SUMMARYThe reported ability of SCID mice to accept xenografts of both human tumours and peripheral blood lymphocytes (PBL) provides the potential for the development of novel immunotherapy models in these animals. This study describes the development of a novel small animal model of human ovarian cancer. This was achieved by engrafting a human ovarian cancer cell line into the peritoneal cavity of immunodeficient SCID 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 metastatic nodules onto the interior surface of the peritoneal wall. Reconstituted 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 development of this type of malignancy in vivo. Furthermore, vaccination of human PBL-SCID mice against Ovan-4 produced tumour-specific human antibodies in the serum of these animals. Animals reconstituted with CD8-depleted PBL exhibited increased serum immunoglobulin levels and produced enhanced anti-Ovan-4 activity after vaccination. Subsequent challenge of these animals with Ovan-4 revealed a further increase in survival time. These results suggest that human antibodies may have a role in immunity against ovarian cancer and could be of therapeutic value in this type of disease.

Immunological Protection against HPV16 E7-Expressing Human Esophageal Cancer Cell Challenge by a Novel HPV16-E6/E7 Fusion Protein Based-Vaccine in a Hu-PBL-SCID Mouse Model

“…19) Our findings also supported by other reports that vaccination with a DC-based vaccine has an inhibitory effects on the growth of human hepatocarcinoma in SCID mice. 20) Thereby, together with other reports, [21][22][23]25) our data shown here support the notion that hu-PBL-SCID mouse model is an in vivo animal system prior to evaluate human immune responses to a range of prophylactic or therapeutic vaccine candidates for cancer immunotherapy. This study, to the best of our knowledge, is the first to demonstrate that the HPV16 mE6D/mE7/TBhsp70D fusion protein-based vaccine is capable of inducing strong immune responses to human esophageal carcinomas in Hu-PBL-SCID mouse model.…”

“…As these animals also readily accept graft of both human lymphocytes to create human PBL-SCID and human tumor cells, engraftment of both these populations to the same animal provides an in vivo model for analyzing immune effector mechanisms active against human malignant disease. The PBLs used to reconstitute Hu-PBL-SCID can be autologous or allogeneic, 17,18,[21][22][23][24][25] although extension of these allogeneic studies to an autologous system is critical.…”

“…17) Since this animal model was originally reported by Mosier et al in 1988, 18) numerous reports have demonstrated that the coengraftment of tumor cells and HuPBLs donated by healthy adult volunteers into SCID mice provides the opportunity to evaluate anti-tumor immune response of human lymphocytes that is more clinically relevant. This animal model has been successfully applied to evaluate the BCGbased vaccine breast cancer vaccine, 19) the DC-based vaccine against human hepatocarcinoma cells 20) and the anti-tumor efficacy against a wide spectrum of human tumors including lymphoma, glioblastoma, head and neck squamous cell carcinoma, lung and ovarian cancer using cytokine-based immunotherapies 17,[21][22][23][24][25] In the majority of these studies, the HuPBLs were allogeneic with respect to the tumor and the allo-anti-tumor response was found to be mediated primarily by CD8…”

Establishment of intraperitoneal transplantation model of cisplatin-resistant ovarian carcinoma cell in scid mice

“…Walker [11] and Schumashe [7] , et al transplanted human ovarian carcinoma cell strain or precipitated cells in ascites into SCID mouse body and the tumor grew well.…”

In vivoanti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune defi ciency

“…Human lymphocytes to be transferred in SCID mice were isolated from the whole blood obtained from healthy adult volunteers as previously described [7][8][9][10][11] . Human peripheral blood lymphocytes (PBL) were isolated by Ficoll-Paque gradient centrifugation under sterile conditions.…”