Affiliations: [a] Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, Saskatoon, Canada | [b] Department of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, Canada | [c] Department of Medicine, College of Medicine, University of Saskatchewan, Saskatoon, Canada
Correspondence:
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Correspondence and reprint requests to: Dr Jim Xiang, Saskatoon Cancer Center, 20 Campus Drive, Saskatoon, Saskatchewan S7N 4H4, Canada.
Abstract: Our previous study showed that the injection of mouse myeloma VKCK/RM4-IFN-τ cells secreting the fusion protein RM4/IFN-τ to syngeneic BALB/c mice resulted in tumor regression in 70% of mice after tumor inoculation. In this study, the VKCK/RM4-IFN-τ cell line was used to characterize the protective immunity subsequent to tumor inoculation. Our histologic findings demonstrated that, in the primary response to VKCKRM4-IFN-τ 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-τ 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-τ 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.
Keywords: Fusion protein, macrophage, CD8+ T lymphocyte, anti-tumor immunity
