Characterization of anti-tumor immunity derived from the inoculation of myeloma cells secreting the fusion protein RM4/IFN-τ

Abstract

Our previous study showed that the injection of mouse myeloma V_KC_K/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 V_KC_K/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 V_KC_KRM4-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 V_KC_K 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 V_KC_K/RM4-IFN-τ cells were able to grow as aggressively as the parental V_KC_K 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 V_KC_K 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.