Development of an experimental murine pulmonary metastasis model incorporating a viral encoded tumor specific antigen

A SV40 murine tumor model was developed and characterized involving intravenous inoculation of BALB/c mice with syngeneic SV40-transformed kidney fibroblasts (mKSA cells). Following intravenous inoculation with mKSA cells, viable tumor cells were recovered from primary organ cell culture of the brain, spleen, lungs, and kidneys of tumor bearing mice. The presence of mKSA tumor cells in these tissues was confirmed by morphological identification and by immunofluorescence directed to SV40 large tumor antigen (T-ag). Additionally, a computer assisted method was used to enumerate and quantitate the size of tumor foci. Tumor foci were observed in the lungs and were quantifiable based on both size and number. The number and size of foci observed in the lungs of tumor bearing mice was dependent on the dose of mKSA cells and time post-inoculation. Ultimately, the tumor burden in inoculated mice was found to be lethal. Quantification of tumor foci in the lung, survival data, and detection of metastasis to organs at sites distal to tumor cell inoculation, provides specific reference points for use in examining the mechanism(s) of the immune response to tumors expressing viral antigen and in evaluating immunologic based therapies within this new SV40 murine tumor model. The methods described herein can be applied for the development of new animal models of metastasis that express viral encoded tumor-specific antigens.