The goal of this study was to explore immunological strategies to increase local and systemic
tumor control in patients receiving
radiation therapy. In previous studies,
interleukin-3 (IL-3) gene expression within murine
tumors was shown to increase their response to irradiation through immune mechanisms. In this study, the efficacy of systemically administered
IL-3 gene-transduced irradiated
tumor cell
vaccines was tested for their ability to augment radiation responses against established immunogenic (FSAR) and nonimmunogenic (FSAN)
tumors.
Vaccines of irradiated FSAR/FSAN or FSAN-JmIL-3/FSAR-JmIL-3 cells were given intraperitoneally just before and after local irradiation of parental
tumors with diameters of 8 mm, as well as in two booster doses. The
IL-3 gene-transduced
tumor cell
vaccines were more effective than the parental
vaccines at delaying
tumor growth after irradiation, although no complete cures resulted. Responses were largely specific to the
tumor type, indicating that
tumor-specific immunity was enhanced by
IL-3 vaccine administration. When the experiment was repeated in the C3H/HeJ mice, which are deficient in
tumor necrosis factor-alpha production, the
vaccines were still effective, but less so than in C3H/HeN mice. Systemic
IL-3 vaccine treatment increased intratumoral levels of
intercellular adhesion molecule-1, Mac-1, EB22/5.3,
tumor necrosis factor-alpha, and
IL-1 mRNA in irradiated
tumors, indicating that cellular infiltration was part of the response. The study demonstrates that local
radiation therapy can enhance the efficacy of genetically altered
vaccine-based
immunotherapy for
cancer by decreasing
tumor burden. At the same time,
tumor cell
vaccines may improve the cure rate of local
radiation therapy by eliminating
residual cancer cells. Although less effective than intratumoral gene expression, administration of
IL-3 gene-transduced
tumor cell
vaccines is clinically a more feasible strategy that may be useful in situations in which the
tumor load is small.