Abstract:
:We have shown that interleukin-12 (IL-12) generated a strong, albeit transient, anti-tumor response, mostly mediated by natural killer (NK) cell. T cell participation, in addition to NK cells, was essential for persistence of the anti-tumor response. Ligation of 4-1BB, a co-stimulatory receptor expressed on activated T cells, is known to amplify T cell-mediated immunity. In this study, we compared the effect of a systemically delivered agonistic anti-4-1BB monoclonal antibody (anti-4-1BB mAb) with intra-tumoral adenoviral-mediated gene transfer of the 4-1BB ligand (ADV/4-1BBL) to liver metastases in a syngeneic animal model of breast cancer. Both treatments induced a dramatic regression of pre-established tumor. When combined with intra-tumoral delivery of the IL-12 gene, both anti-4-1BB mAb and ADV/4-1BBL were synergistic and led to survival rates of 87% and 78%, respectively. The anti-tumor immunity is mainly mediated by CD4+ T cells in IL-12 plus 4-1BB ligand-treated animals, and CD8+ T cells in IL-12 plus anti-4-1BB mAb-treated animals. However, only long-term survivors after treatment with IL-12 and 4-1BBL genes have showed significantly potent, systemic, and tumor-specific T cell-mediated immunity.
journal_name
Gene Therjournal_title
Gene therapyauthors
Martinet O,Divino CM,Zang Y,Gan Y,Mandeli J,Thung S,Pan PY,Chen SHdoi
10.1038/sj.gt.3301687keywords:
subject
Has Abstractpub_date
2002-06-01 00:00:00pages
786-92issue
12eissn
0969-7128issn
1476-5462journal_volume
9pub_type
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