Abstract
Implantation of microencapsulated engineered cells secreting molecules with antineoplastic properties into tumors is a novel approach to cancer gene therapy. In this study, we constructed an engineered tumor cell line, VkCk/RM4-TNF-α, which secreted RM4/TNF-α fusion protein containing the chimeric antitumor antibody, F(ab')2 (RM4), recognizing the tumor antigen TAG72, as well as the TNF-α moiety. The engineered cells were encapsulated into microencapsules. The RM4/TNF-α fusion protein secreted by encapsulated VkCk/RM4-TNF-α cells could be diffused through the microencapsule membrane into the supernatant and exert a cytotoxic effect on L929 cells in vitro. The antigen-specific binding-reactivity of RM4/TNF-α for the TAG72 antigen was confirmed by immunohistochemical staining of rat LMCR tumor cells which expressed TAG72 antigen. Implantation of microencapsules containing VkCk/RM4- TNF-α cells into LMCR tumors in rats induced tumor regression as a result of tumor necrosis formation. Taken together, these data suggest that microencapsulation of recombinant tumor cells secreting antibody/ cytokine fusion protein might be an alternative approach in the treatment of cancers.
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