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Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells

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dc.contributor.author Cirone, P.
dc.contributor.author Bourgeois, J. M.
dc.contributor.author Shen, F.
dc.contributor.author Chang, P. L.
dc.date.accessioned 2010-01-05T21:40:05Z
dc.date.available 2010-01-05T21:40:05Z
dc.date.issued 2004-10-12
dc.identifier.citation Cirone, P., Bourgeois, J.M., Shen, F. & Chang, P.L. Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells. Hum Gene Ther 15, 945-59 (2004). en_US
dc.identifier.uri http://hdl.handle.net/1807.1/815
dc.description http://www.liebertonline.com en_US
dc.description Reproduced by generous permission of the publisher. en_US
dc.description.abstract An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma- bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated. en_US
dc.description.provenance Submitted by Kelly Lee (klee@cbcra.ca) on 2010-01-05T21:40:05Z No. of bitstreams: 1 Chang_2004.pdf: 962632 bytes, checksum: 60634c9458a4d5e2d1c6083241b5c432 (MD5) en
dc.description.provenance Made available in DSpace on 2010-01-05T21:40:05Z (GMT). No. of bitstreams: 1 Chang_2004.pdf: 962632 bytes, checksum: 60634c9458a4d5e2d1c6083241b5c432 (MD5) Previous issue date: 2004-10-12 en
dc.language.iso en en_US
dc.publisher Mary Ann Liebert, Inc. en_US
dc.title Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells en_US
dc.type Article en_US

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