Identification of α-fetoprotein-specific T-cell receptors for hepatocellular carcinoma immunotherapy.
Identification of α-fetoprotein-specific T-cell receptors for hepatocellular carcinoma immunotherapy.
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DOI：
10.1002/hep.29844
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Zhu W;Peng Y;Wang L;Hong Y;Jiang X;Li Q;Liu H;Huang L;Wu J;Celis E;Merchen T;Kruse E;He Y
Hepatocellular carcinoma (HCC) is the major form of liver cancer for which there is no effective therapy. Genetic modification with T-cell receptors (TCRs) specific for HCC-associated antigens, such as α-fetoprotein (AFP), can potentially redirect human T cells to specifically recognize and kill HCC tumor cells to achieve antitumor effects. In this study, using lentivector and peptide immunization, we identified a population of cluster of differentiation 8 (CD8) T cells in human leukocyte antigen (HLA)-A2 transgenic AAD mice that recognized AFP158 epitope on human HCC cells. Adoptive transfer of the AFP158-specific mouse CD8 T cells eradicated HepG2 tumor xenografts as large as 2 cm in diameter in immunocompromised nonobese diabetic severe combined immunodeficient gamma knockout (NSG) mice. We then established T-cell hybridoma clones from the AFP158-specific mouse CD8 T cells and identified three sets of paired TCR genes out of five hybridomas. Expression of the murine TCR genes redirected primary human T cells to bind HLA-A2/AFP158 tetramer. TCR gene-engineered human T (TCR-T) cells also specifically recognized HLA-A2+AFP+ HepG2 HCC tumor cells and produced effector cytokines. Importantly, the TCR-T cells could specifically kill HLA-A2+AFP+ HepG2 tumor cells without significant toxicity to normal primary hepatocytes in vitro. Adoptive transfer of the AFP-specific TCR-T cells could eradicate HepG2 tumors in NSG mice. We have identified AFP-specific murine TCR genes that can redirect human T cells to specifically recognize and kill HCC tumor cells, and those AFP158-specific TCRs have a great potential to engineer a patient’s autologous T cells to treat HCC tumors.
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影响因子：
56.9
作者：
Morgan, Richard A.;Dudley, Mark E.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
82.9
作者：
Klebanoff CA;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP
影响因子：
3.7
作者：
Kim JH;Lee SR;Li LH;Park HJ;Park JH;Lee KY;Kim MK;Shin BA;Choi SY
通讯作者：
Choi SY
影响因子：
11.5
作者：
Butterfield, LH;Ribas, A;Economou, JS
通讯作者：
Economou, JS