Significant tumor regression induced by microencapsulation of recombinant tumor cells secreting fusion protein.
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.
Research Unit, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Meiqing
M
Shi
Siguo
S
Hao
Mabood
M
Quereshi
Xulin
X
Guo
Changyu
C
Zheng
Jim
J
Xiang
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000295:instrumentation* / Q000379:methods*; D004339:Drug Compounding; D051379:Mice; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D023041:Xenograft Model Antitumor Assays
D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha