Abstract | BACKGROUND: RESULTS: We showed that Icon, as a chimeric factor VII and human IgG1 Fc immunoconjugate, could separately induce murine natural killer (NK) cells and activate complement to kill TCA8113 cancer cells in vitro via antibody dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, Icon-NK ADCC had a significantly stronger effect than that of Icon-CDC. Moreover, Icon could completely eradicate established human tongue tumour xenografts in vivo in the CB-17 strain of SCID mice that have functional NK cells at a normal level, whereas it was less effective in SCID/Beige mice that do not have functional NK cells. CONCLUSIONS: We conclude that NK cells are crucial for the efficacy of Icon immunotherapy in the treatment of cancer. The results also suggest that impaired NK level/activity could contribute to the resistance to therapeutic antibodies that are currently under investigation in preclinical and clinical studies.
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Authors | Zhiwei Hu, Jing Li |
Journal | BMC immunology
(BMC Immunol)
Vol. 11
Pg. 49
(Oct 12 2010)
ISSN: 1471-2172 [Electronic] England |
PMID | 20939894
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Immunoglobulin Fc Fragments
- Recombinant Fusion Proteins
- Factor VII
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Topics |
- Animals
- Antibody-Dependent Cell Cytotoxicity
(drug effects)
- Carcinoma, Squamous Cell
(drug therapy, immunology)
- Cell Line, Tumor
- Complement Activation
(drug effects)
- Cytotoxicity, Immunologic
(drug effects)
- Factor VII
(genetics, metabolism)
- Humans
- Immunoglobulin Fc Fragments
(genetics, metabolism)
- Immunotherapy
- Killer Cells, Natural
(drug effects, immunology, metabolism, pathology)
- Lymphocyte Activation
(drug effects)
- Mice
- Mice, SCID
- Neoplasm Transplantation
- Recombinant Fusion Proteins
(administration & dosage, genetics, metabolism)
- Tongue Neoplasms
(drug therapy, immunology)
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