Abstract |
The efficacy of immunotherapy based on natural killer (NK) cells is hampered by intrinsic non-specific cytotoxicity and insufficient activation of NK cells. Here, we confer the T-cell receptor-like (TCR-like) specificity on NK cells, taking advantage of both the innate and adaptive immune arms of the immune response to generate enhanced anti- melanoma activity. The TCR-like antibody (Ab) GPA7 was selected against melanoma-associated gp100/ human leukocyte antigen (HLA)-A2 complex and then fused to intracellular domain of CD3-ζ chain. This fusion construct was incorporated into NK-92MI cell line and expressed as a chimeric antigen receptor on the surface of the cell. The anti-tumour activity of the transgenic NK-92MI-GPA7-ζ cell line was assessed against melanoma in vitro and in vivo. The engineered NK-92MI-GPA7-ζ cells could recognize melanoma cells in the context of HLA-A2 and showed enhanced killing of both melanoma cell lines and primary melanoma. Furthermore, adoptively transferred NK-92MI-GPA7-ζ cells significantly suppressed the growth of human melanoma in a xenograft model in mice. Collectively, these results demonstrate that the TCR-like Ab, GPA7, could redirect NK cells to target the intracellular antigen gp100 and enhance anti- melanoma activity, providing a promising immunotherapeutic strategy to prevent and treat melanoma.
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Authors | Ge Zhang, Rongzhi Liu, Xuekai Zhu, Lei Wang, Juan Ma, Huamin Han, Xiaomin Wang, Ganlin Zhang, Wen He, Wei Wang, Changzhen Liu, Shenghua Li, Meiyi Sun, Bin Gao |
Journal | Immunology and cell biology
(Immunol Cell Biol)
2013 Nov-Dec
Vol. 91
Issue 10
Pg. 615-24
ISSN: 1440-1711 [Electronic] United States |
PMID | 24100387
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, Antigen, T-Cell
- Single-Domain Antibodies
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Topics |
- Animals
- Antibody Specificity
(immunology)
- Cell Line, Tumor
- Cell Proliferation
- Cytotoxicity, Immunologic
- Humans
- Melanoma
(immunology, pathology)
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Protein Multimerization
- Receptors, Antigen, T-Cell
(immunology)
- Single-Domain Antibodies
(immunology)
- Xenograft Model Antitumor Assays
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