期刊
JOURNAL OF IMMUNOLOGY RESEARCH
卷 2015, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2015/482089
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资金
- institutional grant from INSERM
- INCA [PL-0610-3D1616-103]
- Ligue du Rhone
The present work was designed to compare two mechanisms of cellular recognition based on Ab specificity: firstly, when the anti-HER2 mAb trastuzumab bridges target cells and cytotoxic lymphocytes armed with a Fc receptor (ADCC) and, secondly, when HER2 positive target cells are directly recognized by cytotoxic lymphocytes armed with a chimeric antigen receptor (CAR). To compare these two mechanisms, we used the same cellular effector (NK-92) and the same signaling domain (Fc epsilon RI gamma). The NK-92 cytotoxic cell line was transfected with either a Fc gamma RIIIa-Fc epsilon RI gamma (NK-92(CD16)) or a trastuzumab-based scFv-Fc epsilon RI gamma chimeric receptor (NK-92(CAR)). In vitro, the cytotoxic activity against HER2 positive target cells after indirect recognition by NK-92(CD16) was always inferior to that observed after direct recognition by NK-92(CAR). In contrast, and somehow unexpectedly, in vivo, adoptive transfer of NK-92(CD16) + trastuzumab but not of NK-92(CAR) induced tumor regression. Analysis of the in vivo xenogeneic system suggested that the human CH2-CH3 IgG2 used as a spacer in our construct was able to interact with the FcR present at the cell surface of the few NSG-FcR+ remaining immune cells. This interaction, leading to blockage of the NK-92(CAR) in the periphery of the engrafted tumor cells, stresses the critical role of the composition of the spacer domain.
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