PMID- 24100387 OWN - NLM STAT- MEDLINE DCOM- 20140724 LR - 20180822 IS - 1440-1711 (Electronic) IS - 0818-9641 (Linking) VI - 91 IP - 10 DP - 2013 Nov-Dec TI - Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain antibody. PG - 615-24 LID - 10.1038/icb.2013.45 [doi] AB - 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-zeta 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-zeta cell line was assessed against melanoma in vitro and in vivo. The engineered NK-92MI-GPA7-zeta 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-zeta 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. FAU - Zhang, Ge AU - Zhang G AD - 1] The Centre for Molecular Immunology and China-Japan Joint Laboratory of Molecular Immunology and Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China [2] University of Chinese Academy of Sciences, Beijing, China. FAU - Liu, Rongzhi AU - Liu R FAU - Zhu, Xuekai AU - Zhu X FAU - Wang, Lei AU - Wang L FAU - Ma, Juan AU - Ma J FAU - Han, Huamin AU - Han H FAU - Wang, Xiaomin AU - Wang X FAU - Zhang, Ganlin AU - Zhang G FAU - He, Wen AU - He W FAU - Wang, Wei AU - Wang W FAU - Liu, Changzhen AU - Liu C FAU - Li, Shenghua AU - Li S FAU - Sun, Meiyi AU - Sun M FAU - Gao, Bin AU - Gao B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131008 PL - United States TA - Immunol Cell Biol JT - Immunology and cell biology JID - 8706300 RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Single-Domain Antibodies) SB - IM MH - Animals MH - Antibody Specificity/immunology MH - Cell Line, Tumor MH - Cell Proliferation MH - Cytotoxicity, Immunologic MH - Humans MH - Melanoma/*immunology/pathology MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Protein Multimerization MH - Receptors, Antigen, T-Cell/*immunology MH - Single-Domain Antibodies/*immunology MH - Xenograft Model Antitumor Assays EDAT- 2013/10/09 06:00 MHDA- 2014/07/25 06:00 CRDT- 2013/10/09 06:00 PHST- 2013/06/29 00:00 [received] PHST- 2013/08/01 00:00 [revised] PHST- 2013/08/01 00:00 [accepted] PHST- 2013/10/09 06:00 [entrez] PHST- 2013/10/09 06:00 [pubmed] PHST- 2014/07/25 06:00 [medline] AID - icb201345 [pii] AID - 10.1038/icb.2013.45 [doi] PST - ppublish SO - Immunol Cell Biol. 2013 Nov-Dec;91(10):615-24. doi: 10.1038/icb.2013.45. Epub 2013 Oct 8.