Despite evidence that antitumor immunity can be protective against
renal cell carcinoma (RCC), few patients respond objectively to
immunotherapy and the disease is fatal once
metastases develop. We asked to what extent combinatorial
immunotherapy with Adenovirus-encoded murine
TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus
CpG oligonucleotide, given at the primary
tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic
tumor growth in mice, we developed a
luciferase-expressing Renca cell line, and monitored
tumor burdens via bioluminescent imaging. Orthotopic
tumor challenge gave rise to aggressive primary
tumors and lung
metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal
tumors. Intra-renal
immunotherapy also led to systemic immune responses characterized by
splenomegaly, elevated serum
IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung
tumors.
Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary
tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung
tumors. A similar approach may prove beneficial for patients with metastatic RCC.