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Significant tumor regression induced by microencapsulation of recombinant tumor cells secreting fusion protein.

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-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.
AuthorsMeiqing Shi, Siguo Hao, Mabood Quereshi, Xulin Guo, Changyu Zheng, Jim Xiang
JournalCancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 20 Issue 3 Pg. 260-6 (Jun 2005) ISSN: 1084-9785 [Print] United States
PMID15989471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
Topics
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell- and Tissue-Based Therapy (instrumentation, methods)
  • Drug Compounding
  • Mice
  • Neoplasms (metabolism, pathology)
  • Rats
  • Recombinant Fusion Proteins (administration & dosage, genetics, metabolism, toxicity)
  • Tumor Necrosis Factor-alpha (genetics, metabolism, toxicity)
  • Xenograft Model Antitumor Assays

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