Development of a Novel Vaccine with Fusions of Dendritic and Ovarian Cancer Cells from Patients
Abstract
Dendritic/tumor fusion cell vaccine has been developed in our lab. The antitumor immunity induced by fusion cells has been demonstrated in murine models and in humans. In the present study, ovarian carcinoma cells (OVCA) derived from 8 out of 9 patients were successfully fused with autologous DC. The created heterokaryons expressed tumor-associated antigens, such as CA-125, MUC1 or/and HER2/neu, and DC-derived co-stimulatory and adhesion molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. The level of T cell proliferation was increased six-seven folds when cocultured with fusion cells. Significantly, CD4+/CD8+ T cells derived from patients with ovarian cancer were stimulated by fusion cells to secret high level of IFN-r as demonstrated by intracellular staining in 7 patients. The T cells primed by fusion cells produced MHC class l<lependent lysis of autologous ovarian tumor cells. Furthermore, MUC1 -specific CTL were generated from a HLA-A2 patient with ovarian carcinoma positive for MUC1 as demonstrated by MHC class l/MUC1 peptide tetramenc analysis. These findings indicate that fusions of human ovarian cancer cells with autologous DC activate both CD4+ and CD8+ T cells and are associated with potent and antigen-specific antitumor responses against autoloqous ovarian cancer cells
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA418726
Entities
People
- Jianlin Gong
Organizations
- Boston University