Engineered fusion hybrid vaccine of IL-4 gene-modified myeloma and relative mature dendritic cells enhances antitumor immunity.
Dendritic cell (DC)-tumor fusion hybrid vaccine which facilitates antigen presentation represents a new powerful strategy in cancer therapy. In the present study, we investigated the antitumor immunity derived from vaccination of fusion hybrids between wild-type J558 or engineered J558-IL-4 myeloma cells secreting cytokine interleukin-4 (IL-4) and immature DCs (DC(IMAT)) or relative mature DCs (DC(RMAT)). DC(RMAT) displayed an up-regulated expression of immune molecules (Ia(d), CD40, CD54, CD80 and CD86) and certain cytokines/chemokines, and enhanced ability of allogeneic T cell stimulation when compared to DC(IMAT). These DCs were fused with myeloma cells by polyethylene glycol (PEG). The fusion efficiency was approximately 20%. Our data showed that immunization of C57BL/6 mice with DC(RMAT)/J558 hybrids induced protective immunity against a high dose of J558 tumor challenge (1x10(6) cells) in 3 out of 10 immunized mice, compared with no protection seen in mice immunized with DC(IMAT)/J558 hybrids. Furthermore, immunization of mice with engineered DC(RMAT)/J558-IL-4 hybrids elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro and induced more efficient protective immunity (10/10 mice; tumor free) against J558 tumor challenge in vivo than DC(RMAT)/J558 hybrid vaccines. The results demonstrate the importance of DC maturation in DC-tumor hybrid vaccines and indicate that the engineered fusion hybrid vaccines which combine gene-modified tumor and DC vaccines may be an attractive strategy for cancer immunotherapy.
Liu
Yongqing
Y
Research Unit, Departments of Oncology and Pathology, College of Medicine, Saskatchewan Cancer Agency, University of Saskatchewan, 20 Campus Drive, Saskatoon, Saskatchewan, Canada S7N 4H4.
Zhang
Weidong
W
Chan
Tim
T
Saxena
Anurag
A
Xiang
Jim
J
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D005260:Female; D006825:Hybridomas / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D007109:Immunity / Q000187:drug effects*; D015847:Interleukin-4 / Q000008:administration & dosage / Q000235:genetics* / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4