Immunotherapy treatment of mammary and prostate cancer in C3(1)/TAG mice

We have developed a transgenic mouse model for mammary and prostate cancer. The C3(1)/TAG mice, as well as cell lines established from mammary and prostate adenocarcinomas, are being utilized to pursue immunotherapeutic strategies. Three modes of immunotherapy treatment are being employed: systemic injections, direct microinfusions and injection of factor-secreting cell lines. Female C3(1)/TAG mice provide an accessible mammary tumor model with visible tumors arising around 4 months of age. Systemic treatment of these mice with the cytokine combination of IL-2 and IL-12 causes tumor regression. The IL-12/pulse IL-2 regime leads to a decrease in tumor size and total number of tumors per animal. In an effort to avoid potential systemically-induced toxic effects, direct microinfusions are being performed which deliver substances directly into the mammary tumors. Initial studies utilized dyes and radiolabelled proteins in an attempt to understand infusion mechanics in mammary tumor tissue. Infused material accumulates in non-epithelial cell regions of the tumor, possibly due to the exclusion of diffusion by tight junctions between epithelial cells. Direct microinfusion studies of mammary tumors with IL-2 and IL-12 have been initiated. Mammary and prostate tumor cell lines have also been manipulated to produce various cytokines and other factors, including GM-CSF, B7, IL-2 and IL-12 and are being used as tumor vaccines.

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