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.
Research Unit, Departments of Oncology and Pathology, College of Medicine, Saskatchewan Cancer Agency, University of Saskatchewan, 20 Campus Drive, Saskatoon, Saskatchewan, Canada S7N 4H4.
Yongqing
Y
Liu
Weidong
W
Zhang
Tim
T
Chan
Anurag
A
Saxena
Jim
J
Xiang
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