Characterization of anti-tumor immunity derived from the inoculation of myeloma cells secreting the fusion protein RM4/IFN-tau.
Our previous study showed that the injection of mouse myeloma VKCK/RM4-IFN-tau cells secreting the fusion protein RM4/IFN-tau to syngeneic BALB/c mice resulted in tumor regression in 70% of mice after tumor inoculation. In this study, the VKCK/RM4-IFN-tau cell line was used to characterize the protective immunity subsequent to tumor inoculation. Our histologic findings demonstrated that, in the primary response to VKCK/RM4-IFN-tau inoculation, tumor regression is associated with macrophage infiltration. This macrophage-dominated regression further leads to a protective immunity against the 2nd challenge of parental VKCK tumor cells. FACS analysis and chromium release assays showed that the majority of T lymphocytes that mediated this anti-tumor immunity were CD8+ cytotoxic T lymphocytes (CTLs). Our animal studies further showed that the VKCK/RM4-IFN-tau cells were able to grow as aggressively as the parental VKCK cells in T lymphocyte deficient nude mice. The protective immunity started 7 days, became complete 10 days following and lasted up to at least 12 months subsequent to the tumor inoculation. The adoptive transfer of T lymphocyte-enriched spleen cells or CTLs also conferred significant protection against tumor growth of parental VKCK cells (p < 0.01). These data thus support the notion that genetically engineered tumor cells secreting IFN-tau may have potential use as tumor vaccines in preventing the development of tumor recurrence and/or metastases following the surgical removal of the primary tumors.
Qi
Y
Y
Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, Canada.
Moyana
T
T
Chen
Y
Y
Xiang
J
J
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002461:Cell Line, Transformed / Q000276:immunology / Q000637:transplantation; D007111:Immunity, Cellular; D007114:Immunization; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma