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-alpha, which secreted RM4/
TNF-alpha fusion
protein containing the chimeric antitumor antibody, F(ab')2 (RM4), recognizing the
tumor antigen TAG72, as well as the
TNF-alpha moiety. The engineered cells were encapsulated into microencapsules. The RM4/
TNF-alpha fusion
protein secreted by encapsulated VkCk/RM4-
TNF-alpha 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-alpha 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-alpha 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.