Allogeneic tumor-dendritic cell fusion vaccines for generation of broad prostate cancer T-cell responses.
Antigen-loaded dendritic cells (DC) are considered potent stimulators of protective immunity. In some studies, DC hybridized with tumor cells have shown promising antitumor responses in mice as well as in humans. A practical drawback of this approach is the limited availability of autologous tumor samples. We investigated the possibility of hybridizing allogeneic prostate cancer cells with human-monocyte-derived DC, and thereby combine the wide repertoire of antigens from the tumor cells with the costimulatory features of the autologous antigen-presenting cells. Three tumor cell lines were used for hybridization using polyethylene glycol (PEG). We show that all three cell lines formed hybrids with DC to the same extent and without significant loss of viability. Restimulation of autologous T cells with these hybrids resulted in generation of tumor-specific IFNgamma-producing T cells with all three tumor cell lines. Similar tumor specificity could not be obtained if T cells were stimulated using a mixture of non-PEG-fused tumor cells and DC. Moreover, these T cells were capable of specific recognition of other tumor cells of prostate cancer origin and autologous DC pulsed with lysate from these prostate cancer cell lines, while a panel of unrelated EBV-transformed B cell lines were not recognized. These results are strongly indicative of the true tumor specificity of these T cells. Our results suggest that DC hybridized with allogeneic prostate cancer cell lines are potent stimulators of a broad prostate-tumor-specific response.
Cancer Center Karolinska, Immune and Gene Therapy, Department of Oncology and Pathology, Radiumhemmet, Karolinska Institutet, 171 77 Stockholm, Sweden.
Andreas
A
Lundqvist
Andreas
A
Palmborg
Gawa
G
Bidla
Mike
M
Whelan
Hardev
H
Pandha
Pavel
P
Pisa
D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines; D002459:Cell Fusion; D003713:Dendritic Cells; D005434:Flow Cytometry; D006801:Humans; D006822:Hybrid Cells; D007167:Immunotherapy / Q000379:methods; D008297:Male; D009000:Monocytes; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines