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Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Tumor-directed therapeutic approaches require unique or
overexpressed specific Ag or receptor as a target to achieve selective
tumor killing. However, heterogeneous expression of these targets on
tumor cells limits the efficacy of this form of therapy. In this study,
we forced abundant expression of IL-13R
2 chain by plasmid-mediated
gene transfer in head and neck, as well as prostate tumors to provide a
potential target. This was followed by successfully treating xenograft
tumor-bearing nude mice with IL-13R-directed cytotoxin (IL13-PE38QQR).
Although we did not observe an indirect cytotoxic bystander effect
conveyed to nontransduced tumor cells in vitro, our approach in vivo
led to a complete regression of established tumors transfected with
IL-13R2 chain in most animals. We found that the tumor eradication
was achieved in part by infiltration of macrophages and NK cells,
assessed by immunohistochemistry. Moreover, head and neck tumors
xenografted in macrophage-depleted nude mice were less sensitive to the
antitumor effect of IL-13 cytotoxin. Because we did not observe
vector-related toxicity in any vital organs, our novel combination
strategy of gene transfer of IL-13R2 chain and receptor-directed
cytotoxin therapy may be a useful approach for the treatment of
localized cancer.
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